Thrombomodulin (TM) is a constituent glycoprotein of endothelial cell membrane, and soluble TM is present also in plasma and urine. It was revealed by experiments using cultured HUVEC in vitro that TM is released from endothelial cell membrane not with monensin, thrombin, fibroblast growth factor, interleukin-1 or endotoxin, but with H₂O₂ or exdotoxin-treated granulocytes. And the release was suppressed by the coexistense of gabexate mesilate or superoxide dismutase. It was suggested that soluble TM was released from endothelial cell membrane by its injury and digested to multiple molecular forms by endogenous and granulocytic protease (s). TM level in circulation is increased in cases of SLE, MCLS, diabetic angiopathy. It was increased in cases of overt DIC and decreased to the normal level when the patient was recovered from DIC. TM level in circulation was also increased in cases of decompensated liver cirrhosis and markedly in cases of renal insufficiency. It was concluded that plasma TM is a parameter reflecting endothelial injury due to inflammation or metabolic disorders of vascular system. But the interpretation of increased plasma TM was difficult when renal insufficiency was complicated.

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Forty-eight patients with acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes (MDS) were treated with low-dose Ara-C regimen (LDAC) (10 mg/m² or 10 mg/body subcutaneously every 12 hours). Complete remission (CR) was obtained in sixteen patients (33%) and partial remission (PR) in six (16%). Seven of eight patients with hypoplastic leukemia entered CR. However, LDAC was not effective in MDS and ANLL developing from MDS. The rate of CR was 20% in relapsed or refractory ANLL. Relapse was occured in thirteen patients until now. The median duration of remission was 7 months (range: 3∼20 months). Seven of the sixteen patients who achieved CR were received LDAC at the same dose for 10 days every month as a maintenance therapy. The duration of CR of these patients was shown to be longer than that of the patients without any maintenance therapy. Myelosuppression was observed in nearly all of them and the other clinical findings including cytogenetic analysis indicated cytotoxicity rather than differentiation as the mechanism of LDAC. LDAC was effective especially in hypoplastic leukemia and the maintenance therapy was found to prolong the duration of CR.

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From January 1978 to August 1990, Staphylococcus aureus bacteremia (SAB) were identified in 31 patients with hematological malignancies at Jichi Medical School hospital. Mortality due to SAB was 48.4% (15/31). Of the variables analyzed, four factors were significantly associated with a poor prognosis; elderly age (p=0.015), high granulocyte count (more than 500/μl) (p=0.015), presence of DIC (p=0.011) and presence of pneumonia (p=0.023). The incidence of methicillin-resistant SAB was 32.3% (10/31) and the first patient developed in 1985. Although not statistically significant, there was a trend of higher mortality for methicillin-resistant SAB (70%) than for methicillin-sensitive SAB (38.1%). Most strains of methicillin-resistant Staphylococcus aureus were sensitive to minocycline, chloramphenicol and vancomycin.

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We reported some biological properties of HIV-1 isolated from 16 hemophiliac Japanese and accidentaly infected one mother. Peripheral menonuclear cells (PMC_S) were obtained from them, one with AIDS, one with lymphadenopathy and the others were asymptomatic carriers. CD8 depleted PMC_S were obtained by panning methods. They were cocultivated with PHA-stimulated PMC_S from seronegative donors. Fifteen HIV-1 isolates were obtained from 17 cases. Recovery rate was 87.5%. The replication rate of HIV-1 from AIDS patient was faster than other isolates from asymptomatic carriers. They did not from plaques on MT 4 cells. The host range study showed that all fifteen isolates infected primary macrophages and only two simultaneously infected human T cell line (MT 2). None of them showed infectivity to other T cell, B cell or monocytic cell lines. Although our study population was rather small, these results suggested that the majority of seropositive hemophiliac Japanese were already infected by HIV-1 and had the risk for the development of AIDS. Moreover, we recognized that HIV-1 from hemophiliac Japanese showed characteristic biological features, i, e, such as 1) weak cytopathic effects, 2) narrow host rang and 3) tropism to primary macrophages. It is suggested that they may belong to a unique subtype of HIV-1 and their selective infectivity to primary macrophages have some relation to the clinical status of seropositive hemophiliacs. Further study is necessary to clarify these points.

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A 65-year-old man was hospitalized with prolonged fever. The erythrocyte sedimentation rate was 62 mm/hour and the c-reactive protein was 5+. Serum lactic dehydrogenase was 1005 IU with elevation of isozyme types II and III. A computerized tomography scan of the abdomen showed large, bilateral adrenal masses. An aspirated specimen of the bone marrow revealed some clustered atypical cells. These findings suggested the patient had metastatic carcinoma, but the primary lesion could not be found. The patient had an episode of transient unconsciousness in mid course and died of bleeding from the gastrointestinal tract.
A postmortem examination was performed. Microscopic examination showed an accumulation of neoplastic cells in the vascular system throughout the body and their extravascular proliferation in several organs. Immunohistochemical studies were performed on paraffin-embedded fixed tissues. The neoplastic cells were positive with the monoclonal antibodies LCA, LN 1, LN 2 and N 26 but did not show positive staining for factor VIII-related antigen, a marker for endothelial cells. These studies defined the neoplastic cells as being of a germinal-center B lymphocyte origin. On the basis of the above-mentioned results, we suggest that this case may be diagnosed as angiotrophic lymphoma.

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A 29 year-old-man who had been diagnosed as having myelodysplastic syndrome (MDS) in August 1985 was re-admitted to our hospital because of fever and palpitation. His peripheral blood showed severe pancytopenia and bone marrow findings remained to be compatible with MDS (refractory anemia), but karyotype of bone marrow cells revealed 7 monosomy in 17 of 20 metaphases examined. Other laboratory findings revealed decreased serum haptoglobin, positive urine hemosiderin and the normal resistance of red cell membrane. In addition, both Ham test and sugar water test were negative. The titer of cold agglutinin was low, Donath-Landsteiner antibody was not detected. These findings suggested the association of autoimmune hemolytic anemia (AIHA), although both direct and indirect Coombs'test were negative. After administration of 50mg of prednisolone daily, the frequency of red cell transfusion was markedly decreased and transfused red cell life span was prolonged from 10.4 days to 27 days. Afterward, his hematological status rapidly transformed into that of acute nonlymphocytic leukemia about 13 months after admission and he died of gastrointestinal bleeding and cerebral bleeding.
Cases of MDS with immunological disorder have been reported. This is, however, the first case of MDS associated with Coombs negative AIHA.

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The 9-year-old boy was admitted to Shizuoka Children's Hospital because of cervical lymphoadenopathy. Complete blood count showed normal RBC and platelet counts. WBC was 2700/μl with no tumor cells. Bone marrow aspirate showed normocellularity with 34% tumor cells. Lymph node biopsy from his right neck was performed and the patient was diagnosed as non-Hodgkin's lymphoma (lymphoblastic type).
Surface marker analysis disclosed that the tumor cells were positive for CD5, CD7, CD19, CD38, CD71, and Ia antigen. Chromosomal analysis of the cervical lymph node revealed 46, XY, t(7;14)(p15;q32). Molecular investigation with appropriate probe showed germ-line configurations of IgH gene, TcR β gene, and TcR γ gene, and one rearranged band of TcR δ gene. Monoclonality of tumor cells was demonstrated from chromosomal analysis and molecular study.
CD7 and CD19 are not lineage specific antigens because CD7 is expressed on immature AML cells and CD19 is expressed on T ALL cells or AML cells. Moreover, TcR δ rearrangement is considered to occur at early phase of hematolymphoid cells. Based on these data, tumor cells of this patient is considered to originate from immature lymphoid cell, so-called lymphoid stem cell.

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A 51-year-old woman was admitted to our hospital complaining of lymphadenopathy in June, 1987. Lymph node biopsy revealed diffuse lymphoma, mixed cell type according to the LSG classification. On hematological examinations, leukocyte has counted 12,400/μl, of which 15% abnormal lymphocytes containing human T cell lymphotropic virus type-1 (HTLV-1) proviral DNA into the cellular DNA. She was diagnosed as adult T-cell leukemia (ATL). The abnormal lymphocytes in the peripheral blood expressed CD4 but lymph node cells expressed CD8. Thirty months after initial diagnosis, abnormal lymphocytes began to increased and reached 30,500/μl. Surface phenotype of abnomal lymphocytes changed CD3⁺ CD4⁺ CD8^- OKla1⁺ to CD3^- CD4^- CD8^- OKla1^-. This change is considered to show the surface phenotypic diversity in ATL cells.

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We report a rare case who developed pure red cell aplasia (PRCA) and pseudothrombocytopenia associated with hepatitis. A 50-year-old woman was admitted to the hospital because of acute hepatitis A. On the 22nd hospital day, normocytic normochromic anemia without reticulocytosis was developed. A bone marrow aspirate revealed erythroid hypoplasia with a small percentage of proerythroblasts and basophilic erythroblasts, but almost complete absence of polychromatophilic and orthochromic erythroblasts. This case was diagnosed as PRCA characterized by the maturation arrest of erythropoiesis. Anemia was spontaneously recovered following marked reticulocytosis. Afterward, transient EDTA-dependent pseudothrombocytopenia developed for 3 months. The serum taken during the acute phase of PRCA clearly inhibited BFU-E colony formation. This data suggests that some humoral factor in the serum of this patient may be involved in the pathogenesis of PRCA.

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A case of Burkitt's type ALL with numb chin syndrome as the initial manifestation is described. A 57-year-old Japanease male was admitted to our hospital in November 14, 1989 because of paresthesia at the chin and lower lip with diplopia and ptosis. Neurological examination revealed oculomotor paralysis of the right side and hypesthesia on the chin, lower lip and buccal mucous membrane. Laboratory findings showed increased leukocyte count. Bone marrow aspirate revealed hypercellular marrow with 92.3% leukemic cells which had vacuoles in the cytoplasm and surface marker of IgM, κ type. The abnormalities of karyotype included t(8;14). He was treated with chemotherapy and radiation. His conditions were temporarily improved, but relapsed later and died in March 6, 1990. Leukemic infiltrations to the trigeminal nerve were found in autopsy. The relationship between lymphoid malignancies and numb chin syndrome was discussed.

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Hairy cell leukemia (HCL) expressing both surface monocytoid antigen and IgM (κ) was reported. A 62-year-old male was admitted to our hospital in September 21, 1989 because of leukocytosis. Physical examinations showed axillary and inguinal lymphadenopathy but no hepato-splenomegaly. The leukocyte count was 12,600/μl with 73% of abnormal cells like large lymphocytes which had abundant cytoplasm and hairy apperance under phase microscopy. They had ruffles with microvilli under electron microscope. Bone marrow puncture showed normocellular marrow with 71.2% of abnormal cells similar to the peripheral blood. Surface markers were CD11b⁺, CD21⁺, HLA-DR⁺, Tac^- and IgM (κ). They were positive for acidphosphatase staining, but negative for peroxidase and tartrate-resistant acid phosphatase staining. He was diagnosed as Japanese type HCL. HCL expressing both surface monocytoid antigen and IgM is rare and the clinical features of our case are compared with those reported in Japan.

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A 20-year-old man was admitted to our clinic with fever elevation up to 39°C for two months, generalized lymphadenopathy and hepatosplenomegaly. Histological examination of right scalene lymph node with HE staining showed T cell lymphoma-like finding. The patient was given vindesine and prednisolone, and there was almost no clinical improvement. Abnormal large granular lymphocyte appeared in peripheral blood and increased up to 17,000/μl in the terminal stage of clinical course. These lymphocytes had abundant pale cytoplasm with rich large azurophilic granules and a large nucleus with a few nucleoli. The phenotype of these cells were as follows: FcγR+, CD2+, CD5-, CD7-, CD3-, CD4-, CD1-, CD8-, sIg-, CD20-, CD11-, CD13-, OKIa+, CD25-, CD16+, Leu7-. These cells did not have the activity of antibody dependent cellular cytotoxicity but had natural killer activity. The gene of T cell receptor (β and γ chain) did not rearranged in these cells. We concluded that the abnormal cells were derived from natural killer cells, which caused aggressive clinical course.

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The brief record of a 25 y.o. male patient with AML (FAB M1) is shown, in whom the blast cells did not express any of the 5 myeloid antigens or the other-lineage related antigens, as detected with the monoconal antibodies. The blast cells were induced to express CD13 antigen after a short-term culture in vitro. This result suggests that CD13 antigen can be expressed virtually by all AML cells, since CD13 antigen is known to cover fresh AML cells at the highest incidence. No unusual clinical feature was noted in this patient as AML case. The collected documentation of antigen-free AML cases seems necessary for the relevant understanding of AML heterogeneity.

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Natural interferon-alpha (IFN-α) alone was administered to a 42-year-old man with acute leukemia, whose bone marrow revealed hypocellularity (NCC=6×10⁴/μl) and a 50% increase in blasts. Initial chemotherapy regimens, including BHAC-DMP or low dose Ara-C were ineffective. One month after starting nIFN-α therapy, the blasts in his bone marrow decreased below 3% and peripheral blood cell counts became normal. He has been in remission for at least 7 months.

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We investigated plasma levels of plasminogen activator inhibitor 2 (PAI-2) in 40 patients with hematological malignancies including acute leukemia, chronic leukemia, hemophagocytic histiocytosis (HH) and histiocytic sarcoma (HS). The plasma PAI-2 levels in the patients with mononuclear phagocyte system (MPS) proliferative disorders (M4, M5, and CMMoL on FAB classification, HH and HS) were all above the cut-off value in healthy subjects. In a patient of reactive HH, there was a close correlation between Plasma PAI-2 and serum ferritin levels during the clinical course. These results indicate that the increase of plasma PAI-2 would be a diagnostic indicator of MPS proliferative disorders.

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