The kininogen (KGN) gene status was examined in 4 families with both high molecular weight (HMW) and low molecular weight (LMW) KGM deficiency and one family with only HMW-KGN deficiency reported in Japan. No abnormal HMW-KGN or LMW-KGN was detected in those with these deficiencies by immunoblot analysis using monoclonal antibodies (HKG-H12, HKG-L7, HKG-L17) for human HMW-KGN.
HMW-DNA prepared from peripheral blood leucocytes was digested with endonuclease, EcoRI, Bam HI, Hind III, Sca I, Bg1II, Xba I, Msp I, Pst I, Hpa I, PvuII, HaeIII, Rsa I, Alu I or Taq I, and studied by Southern blot analysis with human LMW prekininogen cDNA (phKG 36) as a probe. Agross deletion or insertion of the KGN gene was not detected in those with both HMW- and LMW-KGN deficiencies. On the other hand, partial defect in intron 7 (G) was found in those with only HMW-KGN deficiency, suggesting that this defect might be related to abnormality of the alternative RNA splicing events for HMW-prekininogen mRNA.

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Congenital deficiency of high molecular weight kininogen (HMWK), first reported by Saito et al. in 1975, is a rare disorder with homozygous defect of HMWK and only 14 cases have been reported so far.
Prolonged partial thromboplastin time and depressed intrinsic fibrinolytic activity in plasma interacted with negatively charged surface were characterized in these patients without any bleeding problem. On the other hand, patients associated with hemorragic disorder, such as haemophiliacs, showed a markedly prolonged partial thromboplastin time but normal intrinsic fibrinolytic activity. These results give us a important suggestion on our understanding of why haemophiliacs bleed and why HMWK deficient patients do not.
In immunological studies with specific antisera directed against human plasma HMWK and prekallikrein, HMWK in present in normal plasma in free form and a complexed form with prekallikrein, and whole prekallikrein in present in a complexed form with HMWK. This result is associated with diminished level of prekallikrein in plasma of patients with congenital HMWK deficiency.
According to above-mentioned our experimental results and some reports, it is speculated that the deficiency of HMWK with normal level of prekallikrein is acquired.

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Changes of high molecular weight kininogen (HMW-K) clotting activity, antigen and cleavage in the plasma in the health and various diseases were studied. In 20 healthy individuals clotting activity of HMW-K, as measured by APTT one stage method, was 99±12% (male) and 84±15% (female). Antigen as measured by Laurell method were 106±24% (male) and 91±21% (female). In 35 patients with disseminated intravascular coagulation (DIC), both activity (78±33%) and antigen (69±31%) were statistically lower than those in normal individuals (p<0.01). In DIC both activity and antigen of HMW-K was correlated with serum albumin level. These results suggest that the cause of the lower level of HMW-K in DIC especially with septicemia is the result of lower production rather than consumption. In vivo cleavage of HMW-K was detected in plasma of a patient with septicemia and DIC by immunoblotting. The change of HMW-K was also assessed in other pathological states including liver cirrhosis, collagen disease, cardiopulmonary bypass and pregnant women.

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We studied contact factors and kinin-kallikrein in normal non-pregnant and pregnant women, FXII deficient toxemia and DIC. The results obtained are as follows:
1. The levels of plasma prekallikrein, high molecular weight kininogen, kallikrein inhibitor, and C^-₁ INA were gradually decreased at delivery, and the levels of kallikrein like activity and bradykinin were increased during pregnancy and at the time of parturition. These facts indicate that kinin kallikrein systems played important role in uterine contraction.
2. The levels of contact factors (FXII and FXI) were lower at delivery than those of term.
3. In rat uterus, specific binding of bradykinin was observed by the method of radio receptor assay in the pelet of 10,000×g fetal membranes, and its activity was 38%.
4. A synthetic kallikrein inhibitor (OS-291, MS) and bradykinin antagonist inhibited completely spontaneous uterine contraction of Wistar rats during delivery.
5. In the case of FXII deficency, the levels of plasma prekallikrein, high molecular weight kininogen were normal, but at delivery, these levels were lower than those of term. The levels of kallikrein like activity which was half of normal parturition level was increased at parturition.
6. In cases of DIC (17) and severe toxemia (22), plasma prekallikrein lyevels were lower than the normal controls. The decrease was due to consumption of plasma prekallikrein to kallikrein activation.

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Eighteen patients with DPB and 15 with IIP were studied on the relationship between the deseases and ATL. Anti-ATL antigen (ATLA) antibody and its related reactions were examined using immunofluorescence and Western blotting tequniques. Five of 18 DPB patients (28%) were anti-ATLA antibody positive, and were diagnosed as ATL because of the appearance of ATL cells after the chronic DPB clinical course. No IIP patient was diagnosed as having ATL, however, a patient's serum converted to anti-ATLA antibody positive from ATLA related reaction positive when tested with immunofluorescence. ATLA related reaction with diffuse reaction patterns in both MT-1 and MT-2 cells was detected in 7 of 18 sera in patients with DPB and in 5 of 15 IIP sera. A diffuse pattern only in MT-2 cells was found in 2 cases of DPB and 3 of IIP. Positive percentage of these anti-ATLA antibody and ATLA related reactions in DPB and IIP patients was significantly higher than that in controls.
These results suggest the existence of a specific clinicopathological state namely “HTLV-1 associated bronchiolo-alveolar disoder (HABA)” in some of DPB and IIP.

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Infection of HTLV-1 during childhood may be the most probable cause of leukemogenesis of ATL. The possibility of mother to child transmission of HTLV-1 was studied.
Our epidemiological investigation disclosed that almost all mothers of HTLV-1 carrier children were positive for anti-HTLV-1 antibody and children born from carrier mothers showed statistically higher positive rate for anti-HTLV-1 antibody than control groups.
A large number of HTLV-1 positive lymphocytes were detected in the milk from carrier mother, but not in the cord blood from newborn babies delivered from carrier mothers.
We innoculated the fresh milk collected from carrier mothers into the oral cavity of a common mammoset to prove the oral infection. The marmoset was found to be serconverted and viral antigen expression was detected in short term cultures of its peripheral T lymphocytes. These results suggest that we can prevent the transmission of HTLV-1 by prohibiting the breast-fred by carrier mother.
We have so far followed up 55 children born from carrier mothers but fed with compound milk only. None of the children in this group became a carrier of HTLV-1, whereas breast-fed group was found to have higher incidence of sero-positivity for HTLV-1. Therefor the trial prevention of HTLV-1 transmission is now undertaken in Nagasaki district.

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Profiles of antigens, associated with activation of normal T cells, on adult T cell leukemia (ATL) cells obtained from ATL patients with various clinical stages (acute, chronic, smoldering), were examined. The expressions of Ki 67, OKT 9 and CD 38 antigens were correlated with the spontaneopus ³H-thymidine uptake and also with the severities of the disease. CD 25 and CD 28 antigens were expressed on ATL cells from all clinical stages. A loss of CD 7 antigen was observed in peripheral blood ATL cells. HLA-DR antigen was detected on smoldering and chronic ATL cells, but the antigen was not present on acute ATL cells. Surprisingly, both of these antigens were present on lymph-node ATL cells, which proliferate 15∼50 fold more than peripheral blood ATL cells do. These findings confirmed that ATL cells preferentially proliferate in lymph nodes, and CD 7 and HLA-DR antigens might contribute to the proliferation.
A cDNA named pLD 78 was isolated from a library constructed from the poly (A)⁺RNAs of tumor promoter and mitogen stimulated human tonsillar lymphocytes, using a differential hybridization technique. pLD 78 DNA sequence codes for a polypeptide consisting of 92 amino acid residues, including a putative signal sequence. A computor search with the National Biomedical Research Foundation library showed that this proteis had homologous sequences with several proteins, which are involved in inflammation and tumorigenesis. The highest homology was found with mouse macrophage inflammatory protein (MIP). The expression of LD 78 gene was examined by RNA blot analysis and the synthesis of LD 78 protein was examined by Western blot analysis using a specific antibody (OCT 801) against LD 78 protein. Two out of two acute type ATL cells expressed the gene, and the LD 78 protein was detected both in culture supernatants and in cellular extracts of the ATL cells. The gene expression was not found in chronic type ATL cells. Seven out of 8 acute myelogenous leukemia (AML) cells expressed the gene, while protein synthesis was not detected in these AML cases. A homology, between LD 78 protein and MIP, suggest that the LD 78 protein may play a role not only for proliferation of ATL cells, but also for neutrophilia in ATL.
Above findings suggest that various antigens and factors are involved in activation and/or proliferation of ATL cells

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A high incidence of multiple primary neoplasms has been observed in our patients with ATL in comparison to persons with other forms of hematologic malignancy who we have observed during the past 24 years (1963∼1985). Five of 15 patients with ATL (33.3%) have had at least one other associated neoplasm in comparison to only 44 of 1156 patients with other forms of hematological malignancy (3.8%). The incidence figures for secondry neoplasms associated with the other hematologic malignancies were 4.3% (16/370) for acute non-lymphocytic leukemia (ANLL), 2.2% (2/90) for acute lymphocytic leukemia (ALL), 4.8% (1/21) for acute unclassifiable leukemia, 2.2% (5/225) for chronic myelogenous leukemia, 4.7% (2/43) for chronic lymphocytic leukemia, 5.9% (8/136) for malignant monoclonal gammopathy and 3.7% (10/271) for malignant lymphoma. The incidence of multiple neophasms in patients with ATL in comparison to those with other hematological malignancies was significant (p<0.01 or p<0.001). The neoplasms associated with ATL have been adenocarcinoma of the thyroid or lung, and squamous cell carcinoma of the larynx, lip or lung.
We identified ATL-derived factor (ADF) in the cytoplasm of the secondary neoplasms of the ATL patients by means of indirect immunofluoroscopy and immunohistochemical techniques utilizing anti-ADF antibody. We also identified ras p21 products in these neoplasms by means of p21 ras monoclonal antibody studies.
The possibility that HTLV-I was the cause of the secondary neoplasms thus was investigated. HTLV-I provirus genome was not found in the 4 cases of non-ATL leukemic cells of the patients with anti-HTLV-I antibodies as determined by means of Southern blot analysis utilizing pX DNA probes.
These findings suggest that there is some association between ATL cells and pre-malignant cells through ADF or other unknown factors in the activation of ras oncogenes. Subsequent suppression of host immune defense mechanisms in ATL patients permits evolution of the secondary neoplasm.

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We performed a blood coagulation study during the course of disseminated intravascular coagulation (DIC) in 34 patients with hematological malignancies. Risk factors of DIC such as increasing tumor mass, anti-tumor therapy and severe infections were frequently observed at onset of DIC, and influenced the prognosis of DIC. Before the onset of DIC, the DIC score and FDP value were slightly elevated, and they were significantly increased after the onset of DIC. Before the onset of DIC, the level of fibrinogen was significantly increased but it was decreased after the onset of DIC. These hemostatic abnormalities continued for about 2 weeks. Patients with DIC showing prolonged APTT and PT had a poor prognosis. The abnormalities of PT, FDP, fibrinogen, DIC score, FDP-D-dimer and fibrinopeptide A were significantly greater in DIC than in Pre-DIC defined as the period one week before the onset of DIC. FDP-D-dimer was also higher in Pre-DIC patients than in those without DIC. Although protein S and C 4 b binding protein were not decreased in DIC or Pre-DIC, Protein C activity decreased during the course of DIC, suggesting that FDP-D-dimer and Protein C activity were useful for diagnosis of Pre-DIC and DIC.

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Cytological examination of the cerebrospinal fluid (CSF) was performed in 88 children with acute lymphocytic leukemia at the time of initial diagnosis (54 cases), during (dayl∼15, 17 cases) or after (day 37∼58, 17 cases) the remission induction chemotherapy.
Leukemic cells were found on cytological examination in 23 cases (42.6%), 5 cases (29.4%) and 2 cases (11.8%), respectively, and the incidence of central nervous system (CNS) leukemia had a tendency to decrease during the induction chemotherapy. The follow-up study of 15 cases of CNS leukemia at diagnosis revealed that the leukemic cells in CSF had decreased within 2 weeks and then disappeared after the induction chemotherapy.
These findings indicate the therapeutic effect of induction chemotherapy including prednisolone on subclinical CNS leukemia at diagnosis.

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The chromosome 14q11 anomaly has been reported to be specific to adult T-cell leukemia (ATL) and this anomaly has also been confirmed in preleukemic state of ATL (pre-ATL) patients though the frequency is low. In an attempt to clarify if the same chromosome aberrations could be found also at the stage of HTLV-I carrier and if there is any cytogenetic difference from non-HTLV-I carriers, a cytogenetic study of lymphocytes stimulated with phytohemagglutinin in three HTLV-I healthy carriers and three non-HTLV-I carriers in an ATL family was performed. The results were as follows.
1. In three HTLV-I carriers, 7 of 311 cells examined (2.3%) showed chromosome aberrations, and 4 cells (1.3%) had 14q11 anomaly
2. In three non-HTLV-I carriers, 4 of 260 cells examined (1.5%) showed chromosome aberrations, whereas no cells had 14q11 anomaly.
These findings suggest that 14q11 anomaly is already present at the stage of HTLV-I carrier and seems to be an important cytogenetic clue to the pathogenesis of ATL.

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We studied the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on white blood cell (WBC) count and neutrophil functions in nine patients with malignant lymphoma. The WBC count and absolute neutrophil count were rapidly increased without a nadir phase after chemotherapy. Neutrophil alkaline phosphatase (NAP) scores also markedly increased following chemotherapy in all patients. Phagocytosis of India ink and nitroblue tetrazolium (NBT) reduction were revealed tend to be increased, but not exceeded significantly to normal range. RhG-CSF repaired neutrophil function in patients with decreasing that. Thus, rhG-CSF may be useful for prevention and treatment of infection after chemotherapy.

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We examined activities of procoagulant and fibrinolysis in homogenate of leukemic cells. Procoagulant activity (PCA) was increased in patients with acute myelocytic leukemia (AML) and acute promyelocytic leukemia (APL), but it was significantly decreased in patients with chronic myelocytic leukemia (CML) and adult T cell leukemia In CML, PCA was increased in the blastic phase. Plasminogen activator activity (PLGAA) was also increased in patients with AML, APL and acute lymphocytic leukemia (ALL) associated with disseminated intravascular coagulation (DIC). Elastase-like activity, trypsin-like activity and chymotrpsin-like activity (CTLA) were increased in those with myelocytic leukemia, but they were low in those with lymphocytic leukemia. PCA, PLGAA and CTLA were significantly higher in patients with DIC than in those without DIC. Measurement of procoagulant and fibrinolytic activity in leukemic cells homogenate may be useful not only for studying hemostatic abnormalities but also for classification of leukemic cells.

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A series of 116 patients with MDS consisted of 74 cases of RA, 10 cases of RARS, 14 cases of RAEB, 9 cases of RAEB-T and 9 cases of CMML, were studied on the quantity and morphological abnormalities of megakaryocytes in relation to over all survival and leukemic change. The amount of megakaryocytes was graded into four groups; marked hypoplasia (O), moderate hypoplasia (L), normoplasia (N) and hyperplasia (H), RA cases showed heterogeneous pattern; containing 14 cases (18.9%) of group (O), 18 cases (24.3%) of group (L), 31 cases (41.9%) of group (N) and 11 cases (14.9%) of group (H). RARS, RAEB, RAEB-T and CMML cases were classified into group (N) or group (H). The heterogeneous pattern of RA did not relate to leukemic change, but over all survival tended to be shorter in group (N) cases. A significant number of young female cases of RA were involved in group (O).
Morphological abnormalities of MDS megakaryocytes were classified into five types; I, mononuclear micromegakaryocytes, II, binuclear micromegakaryocytes, III, mononuclear small megakaryocytes, IV, multiseparated-nuclear megakaryocytes and V, megakaryocytes with bizarre nuclei. RAEB and RAEB-T cases uniformly showed marked dysmegakaryopoiesis ranging from type I to V, whereas RA, RARS and CMML cases showed mild dysmegakaryopoiesis. Only five cases (6.4%) of RA cases had type I micromegakaryocytes. Eight RA cases with type I on diagosis or obtaining it during the clinical course tended to develop acute myeloid leukemia (5 cases) or to transform to RAEB sooner or later. In two cases of RAEB in which hematological improvement was obtained with low dose cytosine arabinoside regimen, disappearance of type I micromegakaryocytes was noted. A female case with 5q- anomaly surviving more than 10 years showed marked megakaryocyte hyperplasia and almost exclusively type III and IV megakaryocytes. These findings indicated that pattern of dysmegakaryopoiesis, especially appearance of type I, was closely related to leukemic change in MDS.
Thus quantitative and qualitative evaluations of MDS megakaryocytopoiesis seemed important to understand the further heterogeneity of pathophysiology in MDS subtypes.

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The effects of recombinant human interferon (IFN) alpha-2b and gamma on the bone marrow megakaryocyte progenitors (CFU-Meg) were compared between eight patients in the chronic phase of Ph¹-positive chronic myelocytic leukemia (CML) and five hematologically normal patients. CFU-Meg was assayed in plasma clot culture added with phytohemagglutinin-stimulated leukocyte-conditioned medium as a source of colony stimulating activity. The average count of CFU-Meg colonies formed from the bone marrow of CML patients was 5.5 times that of normal controls. Spontaneous CFU-Meg colonies were grown in seven of eight CML patients, but in none of five controls. Colony formation by CFU-Meg in CML as well as normal bone marrow was suppressed by the two preparations of IFN in a dose dependent fashion. Their suppressive influence on colonies from CFU-Meg was comparable between CML and normal bone marrow at lower concentrations, but was less marked for CML than normal bone marrow at higher concentrations. The formation of CFU-Meg colonies from CML bone marrow was more severely suppressed by IFN-gamma than IFN-alpha-2b. Depletion of either T lymphocytes or adherent cells from the CML bone marrow cells diminished the suppressive effects of IFN-gamma, but had no influence on the effects of IFN-alpha-2b.

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We report a case of acute myelofibrosis (AMF) developing into acute myelomegakaryoblastic leukemia.
A 33-year-old woman was admitted to our hospital because of fever and chest pain. On physical examination, hepatosplenomegaly was not noticed. Pancytopenia and a small number of blast cells were observed in the peripheral blood. Poikilocytosis was not detected. Bone marrow examination revealed dry tap on aspiration, and moderate increase in reticulin fiber on biopsy. The diagnosis of AMF was made. Eight months later, blast cells markedly increased. Surface marker was investigated and MCS-2 (CD13), C17 (CDw41) and P2 (CDw41) were found to be positive. Electron microscopic examination revealed that blast cells were composed of PPO-positive cells and MPO-positive cells. Based on these findings, it was considered that the patient developed acute myelomegakaryoblastic leukemia.
Recently AMF is thought to be a state to have the ability to develop into various types of acute leukemia. Adequate therapy may be required before the development of leukemia.

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In this paper is reported a case of acute biphenotypic leukemia who was treated by chemotherapy and pursued its effect by two color flow cytometry. A 33-year-old male patient was admitted due to fever and general fatigue and diagnosed as acute leukemia by hematological findings. Surface markers were investigated to find positive reaction of Leu 12 (CD19), J 5 (CD10), My 7 (CD13) and My 9 (CD33), in which Leu 12 and My 9 were simultaneously expressed on the same blast cells by two color flow cytometry. He was treated with daunorubicin, enocitabine, mercatopurine, vincristine, and prednisolone to obtain partial remission. Then, he was administered L-asparaginase, doxorubicine, vincristine and prednisolone to reach complete remission. The effect of chemotherapy was investigated by not only bone marrow puncture, but also by two color flow cytometry. From the findings in this case, the two flow cytometry was proved to be a useful tool for not only diagnosis of acute mixed leukemia, aut also the judgement of the effect of treatment.

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A 73-year-old male was admitted because of slight fever. Systemic lymphadenopathy, polyclonal hypergammaglobulinemia, swelling of pancreas and submaxillary gland and progressing pancytopenia probably by immune mechanism were observed. Histological examination of lymph node showed no destruction of the structure and mild capillary proliferation in the follicle centers. Between follicles, many immunoblasts and mature plasma cells which were polyclonal and mild capillary proliferation were recognized. He was diagnosed as having multicentric Castleman's lymphoma. Administration of prednisolone 10 mg per day improved his symptoms and laboratory data. Then he has been followed up. Refering to the literatures, we discussed the relation between multicentric Castleman's lymphoma and the related diseases.

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We described here a seventy-one year-old male, who had repeated disseminated intravascular coagulation related to artheriosclerosis and aneurysm of the aorta, and was successfully treated with self-subcutaneous injection of heparin sodium.
He developed gingival bleeding and purpura in 1977. He was first treated with prednisolone (30 mg/day) and ACTH-Z under the diagnosis of idiopathic thrombocytopenic purpura associated with chronic thyroiditis, since platelet count (0.2×10⁴/μl) was markedly decreased and megakaryocytes in the bone marrow were increased. By the treatment, platelet count recovered to 16.7×10⁴/μl, while fibrin-degradation product levels were increased and hypofibrinogenemia developed, suggesting disseminated intravascular coagulopathy. Additional treatment with heparin was effective, and the coagulation studies became normal. In 1980, he again developed the episode with thrombocytopenia. At this time, prednisolone did not improve the episode, but heparin was effective. Since 1983, an enlargement of abdominal aorta had been recognized and gradually progressed. In 1983, he developed lumbago and abdominal pain, and received an emergency operation using artificial Y-graft vessel under the diagnosis of rupture of the aneurysm. There was no evidence of consumption coagulopathy at that time. He had been well until 1987, when he developed the third episode of thrombocytopenia with gingival bleeding. Thrombocytopenia was controlled with the treatment of heparin, but needed a continuous treatment with heparin. Thereafter, he has been well managed with self-injection of the anticoagulant, heparin sodium.

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A 30-year-old man was admitted to our hospital because of fever and cervical lymphadenopathy. Hematological examination revealed leukocytosis with atypical lymphcyes in peripheral blood. Mature histiocytes with erythrophagia were detected in the bone marrow. GOT and GPT were elevated. Anti-EB virus antibody titer was high. The titers of VCAIgM and VCAIgG on admission were 1: 320 and 1: 160, respectively, and those at convalescene stage were 1:<10 and 1: 640.
The diagnosis of virus associated hemophagocytic syndrome (VAHS) due to EB virus was made. Immunosuppressive and cytotoxic therapy are thought to be contraindicated in the treatment of VAHS. In this case only a febrifuge was administrated and the condition of the patient was improved.

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A 71-year-old woman was hospitalized because of hematemesis on December 1, 1987. Her white blood cell (WBC) count was 41,200/μl with 48% of lymphoblasts, and the bone marrow was hypercellular with more than 90% of blasts. The diagnosis of acute lymphoblastic leukemia (ALL) (FAB: L3) was made by morphologic, cytochemical and immunologic studies of the blasts. The examination of fiber gastroscope revealed remarkable varix in the stomach, suggesting portal hypertension accompanied by infiltration of leukemic cells into reticulo-endothelial system. She died of respiratory failure because of bleeding into the trachea. The autopsy disclosed the massive infiltration of leukemic cells into the whole organs. In the chromosome study of the peripheral blood, t(2;8) and 14q+ were observed, and these chromosomal abnormalities are relatively unusual in patients with Burkitt's lymphoma.

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A spontaneous complete remission of 5 month's duration was observed in a 70 year-old man with acute myeloblastic leukemia complicated with severe pneumonia. The remission occurred after severe pancytopenia. He was treated only with antibiotics and blood transfusions. On admission, the leukocyte count was 6.4×10³/μl with 98% myeloblasts. The hemoglobin level was 9.9 g/dl and platelet count was 1.5×10⁴/μl. Marrow aspirate was hypercellular with 98.5% myeloblasts, which weakly showed Ia like antigen and myeloid related antigen. On relapse after five weeks' complete remission, leukemic cells were more immature, peroxidase negative and showed no surface markers. Chromosomal abnormalities were detected. During remission induction therapy he died of severe bacterial and fungal sepsis. Such cases of spontaneous complete remission have been rarely reported, previous adult cases were summarized and the role of etiologic factors were discussed.

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After 4 years of chronic phase, a 22-year-old female with Ph¹ (+) chronic myelogenous leukemia developed myelomonocytic crisis. On admission, her Hb was 9.9 g/dl, Plt 4.1×10⁴/μl, WBC 138,000/μl with 16.5% blasts. Bone marrow contained 38% blasts. She received a combination chemotherapy of mithramycin and dorxyurea, as reported by Koller et al. Dose of mithramycin was reduced to 20 μg/kg. Following 1st and 2nd influsions of mithramycin, severe nasal bleeding was seen. Prednisolone 10 mg/day was given from the 3rd dose of mithramycin with apparent hemostatic effects. Calcium gluconate 3 g/day was administered concomitantly. Her disease responded promptly to this treatment and hematological remission was achieved.

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A 69-year-old man was admitted for the evaluation of leukocytosis with atypical cells. Physical examination revealed marked hepatosplenomegaly. The peripheral blood demonstrated Hb 10.1 g/dl, platelet 13.6×10⁴/μl, and WBC 14200/μl with 76% lymphoid cells. Bone marrow showed 52.4% lymphoid cells. These cells had a nucleus which was relatively large with a coarse chromatin structure and one prominent nucleolus. Under electron microscopy, these cells had a narrow cytoplasm containing a few mitochondria with some microvilli.
The surface of these cells was positive for Ia, B₁, B₂, C₃R, and had markedly elevated IgM-K and IgD-K surface immunoglobulins.
Levels of IgG, IgA and IgM were 1140 mg/dl, 53 mg/dl, and 198 mg/dl respectively. He was diagnosed ashaving B-PLL, and was treated with vincristin, cytarabin and prednisolone.
Since B-CLL frequently in accopanied by reduced levels of one or several immunoglobulins, and the most significant is the decrease of IgA, it is speculated from our case that B-PLL is very similar to B-CLL in the abnormalities of B cell function.

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A 60-year-old man born in Okinawa was admitted to our hospital because of epigastralgia. Physical examination revealed general lymphadenopathy, mild hepatomegaly and skin eruption. The peripheral blood leukocyte count was 168,600/μl, with 93% abnormal lymphocytes showing convoluted or lobulated nuclei. Anti HTLV-1 antibody was positive with titer of 1:1280 (PA). Leukemic cells had typical ATL cells' surface markers (OKT3; 97.2%, T4; 93.3%, T8; 2.8%, OKIA1; 39.6%, IL-2R; 41.8%) and complete monoclonal HTLV-1 provirus DNA. Endoscopic examination with biopsy revealed massive involvement of ATL cells into gastric mucosa.
In the course of the treatment, he had extremely massive melena, and was saved by emergency operation. Multiple ulcers were found in the resected colon. Histological examination showed the marked infiltration of the ATL cells into the mucous or submucous membrane. Thereafter, he was treated well with ALG (Anti Lymphocyte Globulin), until hypercalcemia occured.
He died of acute renal failure after hypercalcemia.

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A 12-year-old boy was referred to our hospital because of anemia and jaundice. On admission bone marrow smears were compatible with M6 classification of the FAB, revealing 74.5% erythroblasts of all nucleated cells and 40% blasts of nonerythroid cells. Karyotype analysis revealed 46, XY. Gene rearrangement within the breakpoint cluster region (bcr) on chromosome 22 was negative at this time. Complete remission was attained by a combination chemotherapy. However, at 10 months of remission, cytogenetic studies of the bone marrow demonstrated Ph¹ positive (10%). One month later, the patient fully relapsed with a 75% Ph¹ positive karyotype associated with positive bcr. Subsequently, the patient died of refractory leukemia.

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A 27-year-old woman was admitted to our hospital complaining of purpuras and legs' edema in the 38th week of pregnancy. On admission, the hemoglobin was 7.8 g/dl, platelets 20,000/μl and WBC 6,600/μl with 52% blast cells. Bone marrow aspirate demonstrated 77.2% myeloblasts with prominent Auer rods, consistent with acute myelogenous leukemia.
Receiving packed-red-cell and platelet transfusions, she delivered a normal male infant in the 39th week of pregnancy by normal labor.
After delivery, she was placed on a combination chemotherapy of BHAC-MMP, subsequently DNR added. Four weeks later, a complete remission was obtained, lasting for almost one year, and her child has grown well without hematological disorder. Microscopic findings of the placenta obtained at delivery revealed no invasion of leukemic cells, but 9% blast cells were present in the placental cord blood.
We reviewed 18 cases reported in Japan of acute leukemia in gestational period, that could obtain complete remission and keep the children growing well. Placental transmission of leukemic cells from mother to infant was discussed.

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A 58-year-old male with a 10-years history of thymoma was admitted to our hospital because of the respiratory idfection. Hepatosplenomegaly and systemic lymphadenopathy were revealed on physical examination. Chest rentgenogram showed a large anterior mediastinal tumor and a right pleural effusion. Blood examination showed Hb 11.5 g/dl, leucocyte count 1,600/μl (1% neutrophils, 34% monocytes, 65% lymphocytes) and platelét count 11.2×10⁴/μl. The lymphocytes in the peripheral blood and pleural fluid were mostly small agranular mature lymphocytes and CD2⁺ 3⁺ 4^- 8⁺. A monoclonal rearrangement of TCRβ chain gene was found using Southern blot analysis of the lymphocytes in the peripheral blood and pleural fluid. The CFU-GM colony formation by bone marrow cells was normal, and not suppressed by the patient's serum or peripheral blood lymphocytes. Neutrophil-associated IgG was increased with a direct immunofluorescence test. Serum IgG level was slightly decreased.
Radiation therapy for thymoma exerted no effect. Treatment with prednisolone 60 mg daily resulted in complete disappearance of the pleural effusion and partial improvement of hepatosplenomegaly, thymoma and neutropenia. Histological examination of the thymoma revealed predominantly spindle cell type. He is still in good condition 21 months after diagnosis. This case seems to represent neoplastic proliferation of mature CD8⁺ T cells associated with thymoma.

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We reported a 68-year-old woman with acute nonlymphocytic leukemia, in whom the leukemia transformed from poorly differentiated myeloperoxidase (MPO)-negative type into myelomonocytic type during the observation without chemotherapy. Hematological findings on admission revealed a leukocyte count of 3,500/μl with 48% blasts and a platelet count of 9.2×10⁴/μl. Bone marrow aspiration showed 68.2% infiltration of blasts negative for MPO. Sudan black B and esterase stains. By electron microscopy MPO was detected in the endoplasmic reticulum and nuclearenvelope of the blasts. Large vacuole-like granules were MPO-negative. She was observed without administration of any antileukemic agent or an immunopotentiator. The leukocyte count rose gradually, in association with increases in the relative and absolute counts of mature neutrophils and monocytic cells, and the platelet count. Twenty-six months after the initial diagnosis, a blood examination showed a leukocyte count of 74,300/μl with 20.5% mature neutrophils and 15.5% monocytic cells, and a platelet count of 31.4×10⁴/μl. Cytological, cytochemical, ultrastructural and immunological studies of the bone marrow cells showed features compatible with acute myelomonocytic leukemia (FAB M4). This case is unusual in respect that poorly differentiated ANLL transformed spontaneously into moderately differentiated ANLL.

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We reported a case of chronic B-cell leukemia reacted to the administration of 1 α (OH) D₃ (Alfarol-CHUGAI Pharm. Co.), The patient showed pancytopenia with IgM-κ type monoclonal protein in the serum. The bone marrow aspiration was failed due to a dry tap, but the biopsied specimen showed a marked infiltration of small sized lymphoid cells with wide cytoplasm. The leukemic cells from peripheral blood showed a morphology of atypical hairy cells, Surface markers of the leukemic cells were IgM, D (κ)⁺, CD 19⁺, CD 20⁺, CD 21^- and HLADR⁺, The leukemic cells showed no L-tartarate resistant acid phosphatase sensitivity. This case was diagnosed as a chronic B-cell leukemia closely related to a hairy cell lyeukemia.
The treatment with estrogen-chrorambucil compound (Bestrabucil-KUREHA Chem, Co.) or splenic irradiation was not effective. However, after two months' administration of Alfayrol the regular blood transfusion was not needed because of increment of the Hb concentration. After eight months of its administration, the bone marrow aspirate showed a marked decrease in the number of the leukemic cells and a restoration of normal hematopoietic cells.
This experience suggested that Alfarol in usefull for the treatment of chronic B cell leukemia including hairy cll leukemia and chronic lymphocytic leukyemia.

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A 67-year-old man was admitted to our hospital with abdominal distension due to hepatosplenomegaly. The peripheral blood revealed Hb content 6.5 g/dl, platelet count 4.7×10⁴/μl, and WBC count 105.8×10³/μl with 88% of mature neutrophils. The neutrophil alkaline phosphatase score was 421. Bone marrow aspiration revealed hypercellularity with increased megakaryocytes and myeloid hyperplasia. 46, XY, del 20(q 11) without Philadelphia chromosome was identified by cytogenetic study.
The patient was diagnosed as having chronic neutrophilic leukemia and was successfully treated with busulfan, but he died of atypical mycobacteriosis about 20 months later. Analysis of neutrophil function demonstrated diminution of deformability, random mobility, and chemotaxis, but almost normal phagocytosis and bactericidal capacity. Southern analysis showed no rearrangements of breakpoint cluster region (bcr) gene and immunoglobulin heavy chain gene.

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Multiple myeloma associated primary biliary cirrhosis (PBC) is very rare and only two cases have been reported. In this paper, we reported the first case of male patient with asymptomatic PBC and multiple myeloma.
A 66 year-old Japanese male was referred to our hospital for the further examination of a monoclonal gammopathy. He was diagnosed of multiple myeloma (IgG-lambda type) because of 2.3 g/day of Bence Jones proteinuria (lambda type), 3,401 mg/dl of monoclonal IgG (lambda type), 12.8% of bone marrow plasmocytosis and generalized osteoporosis. The alkaline phosphatase was 314 mU/ml and serum IgM level (polyclonal) 937 mg/dl. The patient was started on intermittent courses of melphalan and prednisolone, achieving transient improvement. After two years, hepatosplenomegaly developed gradually and the levels of serum ALP elevated increasingly. At that time, relevant investigation results were: serum ALP 663 mU/ml, serum IgG 4,144 mg/dl, serum IgM 823 mg/dl, positive anti-mitochondrial antibody test ×320. The liver biopsy showed chronic nonsuppurative destructive cholangitis. PBC (stage 1∼2 according to Sheuer's criteria) associated with multiple myeloma was diagnosed. A pathogenetic relationship such as loss of immunoregulatory function could be speculated although the simultaneous occurrence of PBC and multiple myeloma could be coincidental.

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We report a rare case of fulminant autoimmune hemolytic anemia (AIHA) with multiple organ failure (MOF). A 40-year-old man was emergently admitted to our hospital because of conscious disturbance and jaundice. The peripheral blood revealed RBC 68×10⁴/μl, Hb 3.5 g/dl, Ht 8.9%, Ret 30‰ (20,400/μl), WBC 20,300/μl, Plts 16.9×10⁴/μl, indirect bilirubin 9.4 mg/dl. Both direct and indirect Coombs test were positive and the IgG autoantibody was identified. Bone marrow aspiration revealed hypercellularity with increased megakaryocytes and erythroid hyperplasia.
The patient was diagnosed as having idiopathic warm type of AIHA and the therapy was started with prednisolone 80 mg/day from the first day of admission but hemolysis with reticulocytopenia was so rapidly progressive that he was in acutely life-threatening state and MOF (acute renal failure, adult respiratory distress syndrome, congestive heart failure, liver dysfunction, rhabdomyolysis) appeared on the third hospital day.
Plasma exchange therapy and hemodialysis were started and high dose methylprednisolone was given soon after rapid administration of sufficient blood transfusion. Dramatic improvement of hemolysis was noted and MOF was controlled after starting these therapies, but he died of exacerbation of MOF probably due to sepsis 40days later.

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A 42-year-old woman was diagnosed as having acute myelogenous leukemia (M 2 of FAB classification) in May, 1985. Complete remission was achieved with the BHAC-DP therapy (BHAC, daunomycin and predonisolone). Whole skull irradiation and intra thecal chemotherapy were performed by way of prevention.
In 1986, she developed her visual disturbance and paraplegia. Myelography and metrizamide CT indicate intraspinal and meningeal infiltration of leukemic cells in the upper thoracic spine. Leukemic cells were found in the cerebrospinal fluid but not in the bone marrow. Complete remission was obtained by irradiation and intrathecal chemotherapy
In Dec. 1986, Ommaya tubing was repeated. Hematological and neurological examinations showed no evidence of malignancy for 3 years. In Oct. 1988, she admitted to our hospital for the maintenance of the remission state, and died of sepsis. The result of autopsy revealed no leukemic cells in her CNS. It is said the intraspinal infiltration of leukemic cells is ratier rare. As it is said the intrathecal injection of anti-leukemic agents is not effective for the intraspinal infiltration, irradiation should be needed. Therefore it is very important to critically differentiated intraspinal from meningeal infiltration. Futhermore, Ommaya tubing is effective in order to maintain remission in a patient with CNS leukemia.

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