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A 59-year-old Japanese woman developed diabetes mellitus without ketoacidosis in the presence of glutamic acid decarboxylase autoantibody (GADA) (24.7 U/mL). After the amelioration of her hyperglycemia, the patient had a relatively preserved serum C-peptide level. Her endogenous insulin secretion capacity remained almost unchanged during 5 years of insulin therapy. The patient's GADA titers normalized within 15 months. The islet-related autoantibodies, including GADA, are believed to be produced following the autoimmune destruction of pancreatic beta cells and are predictive markers of type 1 diabetes mellitus. Therefore, the transient appearance of GADA in our patient may have reflected pancreatic autoimmune processes that terminated without progression to insulin deficiency.

We herein report the case of a 66-year-old Japanese man with acute-onset type 1 diabetes mellitus (T1D) accompanied by pernicious anemia. After 2 weeks of polyuria, the patient developed insulin-deficient hyperglycemia with diabetic ketoacidosis in the absence of verifiable islet-related autoantibodies and began insulin therapy in 2001. Eight years later, he developed gastric autoantibody-positive pernicious anemia and began methylcobalamin treatment. Previous studies have reported cases of slowly progressive autoimmune T1D concomitant with pernicious anemia. The present case suggests that potential associations with organ-specific autoimmune disorders should be considered during the long-term follow-up of T1D patients, even though verifiable islet-related autoantibodies are undetectable.

In order to clarify the relationship between myelodysplastic morphologic features of marrow cells and prognoses and 1.0 define other prognostic factors, 124 patients with the FAB criteria of myelodysplastic syndrome (MIX) were analysed. These included 57 patients with refractory anemia (RA), 5 RA with ring sideroblasts (RARS), 25 RA with excess of blasts (RAEB), 14 chronic myelomonocytic: leukemia (CMML) and 23 with RAEB in transformation (RAEB in T). Univariate analysis of all MDS patients or those of RA demonstrated that the following factors, which were not reported or fully investigated previously, were significantly associated with prognosis. These included neutrophil alkaline phosphatase (NAP) score (significant only for all MDS), the percentage of marrow erythroblasts and lymphocytes present, the percentage of cells with morphological abnormalities in individual cell lineages and the number of cell lineages showing atypia (significant for all MDS and RA). Multiple regression analysis showed that (%) of marrow erythroblasts, NAP score, hemoglobin levels and number of marrow granulocytes with atypia were significant for predicting the prognosis of all MDS patients while the number of marrow megakaryocytes and granulocytes with atypia were significant for prognosis in the subgroup with RA.

A 65-year-old Japanese man presented to our hospital in June 2013 with a 6-day history of fever and fatigue, a 24-h history of thirst, and polyuria. His temperature was 37.8°C and he was alert. However, laboratory tests revealed severe hyperglycemia, undetectable C-peptide levels, and diabetic ketoacidosis. Serum antibody testing confirmed a Coxsackie virus A2 infection. A variety of viral infections are reported to be involved in the development of fulminant type 1 diabetes mellitus (FT1D). Our patient is the first reported case of FT1D associated with Coxsackie virus A2 infection and supports the etiological role of common viral infections in FT1D.

This retrospective analysis investigated the prognostic value of monitoring the response to imatinib using peripheral blood (PB) samples and the impact of the response on outcome in 133 patients with chronic myeloid leukemia (CML). We divided the response into 3 categories according to the results of neutrophil (N)-FISH and BCR-ABL transcript levels in PB; more than a 3-log reduction [major molecular response (MMR)], between a 2-log and 3-log reduction or negative with N-FISH [complete cytogenetic response equivalent (CCyRe)], N-FISH positive or less than a 2-log reduction (non-CCyRe). The median follow-up was 5.46 years. At 5 years, the overall survival (OS) rate and progression-free survival (PFS) rate were 94.4 and 92.0%, respectively. The estimated rate of the CCyRe and MMR were 81.7 and 67.1%, respectively. 106 patients achieving the CCyRe had significantly better OS and PFS than 27 patients without achieving the CCyRe. Patients with MMR had significantly better survival free from death, progression, imatinib withdrawal and a loss of the CCyRe, than patients whose response level remained in the CCyRe without achieving MMR until 18 months. Our observation suggests that the response level of the CCyRe on PB serve as a prognostic indicator, and achieving MMR provides stable long-term survival.

Splenic marginal zone lymphoma (SP-MZL) is a rare low-grade B-cell neoplasm that often shows leukemic manifestation. Less than 20% of cases of SP-MZL express CD5. We analyzed 11 cases of CD5-positive SP-MZL with leukemic manifestation. The clinical characteristics of these cases did not differ from those of CD5-negative SP-MZL. Flow cytometry revealed positive results as follows : CD3, 0/9 ; CD5, 11/11 ; CD10, 0/11 ; CD11c, 4/10, CD13, 5/11 ; CD19, 11/11 ; CD20, 10/11 ; CD21, 4/4 ; CD22, 7/7 ; CD23, 5/10 ; CD25, 8/11 ; FMC7, 5/7 ; κ type 6/9, and λ type 2/9. All 3 cases with monoclonal γ-globulinemia expressed CD13. Resected spleen exhibited a proliferation of neoplastic cells in white pulp in all 8 splenectomy patients and a marginal pattern was detected in 5 patients. Only 2 cases showed involvement of red pulp. Immunohistochemistry showed that the lymphoma cells were positive for CD5, CD20, and BCL-2 and negative for CD3, CD10, cyclin D1, BCL-6, and MUM-1 in all 11 cases. These results suggest that CD5-positive SP-MZL differs from B-cell chronic lymphocytic leukemia, that CD13 expression is found in about half of CD5-positive SP-MZL cases, and that CD5-positive SP-MZL may be related to memory B-cell neoplasm or plasma cell differentiation.

A case of de novo acute hepatitis B that showed symptoms of general malaise and anorexia during rituximab therapy with the CHOP regimen for diffuse large B cell lymphoma is reported. Lamivudine was strikingly effective, showing a rapid recovery from liver damage with jaundice. Hepatitis B virus (HBV) DNA in serum became and stayed undetectable even after the withdrawal of lamivudine, although HBsAg remained positive over 42 months from the onset. Liver biopsy showed a picture suggestive of acute viral hepatitis with multinucleated giant hepatocytes and CD38-positive plasma cell infiltration into liver parenchyma. Immunohistochemically, CD3-positive T-cells were predominant cells that infiltrated in liver parenchyma, whereas CD20-positive B cells were essentially null. Hence, it is suggested from these findings that B lymphocytes might be crucial for the continuous latency in HBV infection and may give rise to de novo acute hepatitis B if totally deleted. Moreover, the CHOP regimen might have some additive effects with the repeated on-off use of corticosteroids to the onset of the disease. In addition, significance of plasma cell infiltration in this setting is discussed.

Seven cases of myelodysplastic syndrome with myelofibrosis, which is defined using the following criteria: (1) pancytopenia with less than 5% blasts in the peripheral blood; (2) minimal or no splenomegaly; (3) myelofibrosis with cellular marrow; (4) absence of diffuse proliferation of blasts in the bone marrow; and (5) presence of myelodysplastic features of bone marrow or peripheral blood cells, are presented. They were in the range of 52-82 years old and consisted of 3 males and 4 females. Six out of 7 cases developed into acute leukaemia after 5 to 8 months from the onset and died from between 2 weeks to 8 months from the evolution to leukaemia. The type of leukaemia was acute myeloblastic in 3 patients, and acute myelo-megakaryoblastic in 3 patients. Another patient died of severe hepatic injury after 5 months from the onset of the disease. These findings revealed that the complication of myelofibrosis in the patients with myelodysplastic syndrome was an indicative sign of rapid progression to overt leukaemia or otherwise poor prognosis for survival. In addition myelodysplastic syndrome is thought to be major primary disorder for acute myelofibrosis. Myelodysplastic syndrome with myelofibrosis is closely associated with the neoplastic proliferation of megakaryoblasts in a considerable number of patients.

A 52-year-old male was diagnosed as having acute promyelocytic leukemia (APL) in 2006. He received induction chemotherapy including all-trans retinoic acid and initially achieved a complete remission (CR). After several courses of consolidation therapy combining anthracyclines and cytarabine, he maintained CR. In 2009, an APL relapse was diagnosed, and he was treated with arsenic trioxide. Since he achieved a second CR, he underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) with a conditioning regimen consisting of busulfan and melphalan. At four months after auto-PBSCT, he developed a pneumothorax and acute respiratory failure. He died despite intensive therapy. Autopsy findings included various atypical and apoptotic cells in his pulmonary tissue. These changes were confirmed in multiple organs throughout the body, suggesting them to be drug-induced. The findings in this case suggested multiple organ failure due to alkylating agents.

Cord blood transplantation (CBT) is being increasingly performed in adults and is now becoming a standard therapeutic alternative to bone marrow transplantation; however, graft failure is one of the associated problems of CBT in adults. A 44-year-old woman with acute myelogenous leukemia in partial remission received an unrelated CBT. Suspected veno-occlusive disease developed, however, and hemopoietic recovery was delayed. A bone marrow examination on the 27th day revealed empty marrow with a relative increase in macrophages, and the serum ferritin concentration was extremely high. Impending failure of the graft due to a hemophagocytic syndrome-like condition was strongly suspected, although donor cells were dominant according to a fluorescence in situ hybridization analysis. A second CBT was performed on the 30th day after a preparatory regimen of methylprednisolone and low-dose fludarabine (total dose, 90 mg/m2). Unexpectedly, the the first donor's cells recovered on the fourth day after the second CBT; however, the cells to finally engraft were those of the second donor. This case is informative as an example of rescue management for suspected graft failure.

A 16-year-old boy in a second remission of acute lymphoblastic leukemia (ALL) had undergone transplantation of bone marrow from an unrelated donor. The conditioning regimen consisted of high-dose cytarabine, etoposide and 12 Gy of total-body irradiation. Although the donor marrow was rejected, hematopoiesis by the recipient himself recovered and he has remained in complete remission for more than 8 years after stem cell transplantation (SCT). Bone marrow karyotype analysis 1 month after SCT showed random chromosomal aberrations. Although complete remission was maintained, various chromosomal aberrations were detected in marrow cells, and in peripheral blood cells under phytohemagglutinin stimulation over 8 years. Moreover, a clone including del(20)(q11) appeared in marrow cells 7 months after SCT and thereafter was also detected 5 years later in the peripheral blood. This persistence of various chromosomal aberrations and a stable clone without evolution to myelodysplastic syndrome or leukemia support the multi step theory of leukemogenesis.

We report the first case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with cytomegalovirus (CMV) infection. A 32-year-old woman was admitted to our hospital because of pandysautonomic signs and symptoms. Thrombocytopenia and hyponatremia were present. Serum anti-CMV IgM and IgG antibodies were positive. Despite hyponatremia, urinary osmolality exceeded plasma osmolality and plasma vasopressin levels related to plasma osmolality were high. Restriction of water intake and administration of dimethylchlorotetracycline improved hyponatremia, suggesting this patient had SIADH. In this patient, SIADH may have been caused by acute pandysautonomia that developed following CMV infection.

We report here the case of a 32-year-old woman who suffered from a unique angiopathy in the central nervous system (CNS). She died of multiple infarcts in the brain stem and cerebellum during treatment with cyclosporine A after bone marrow transplantation for refractory anemia with excess of blasts. The autopsy findings showed segmental narrowing of the basilar artery, in which circumferential dissection of the internal elastic lamina had occurred. The distal portion of the basilar artery was obstructed by upward dislocation of the dissected intima. Similar angiopathy was also observed at multiple sites along the basilar artery branches. These findings suggest endothelial damage, including vasoconstriction and dissection of the CNS arteries.

A 28-year-old Japanese woman with suspected essential thrombocythemia (ET) had marked thrombocytosis, mild leukocytosis with normal neutrophil alkaline phosphatase activity, and no anemia. She was monitored without being given any medication. Eleven years later, complete blood counts showed no remarkable changes but some non-lobulated mononuclear megakaryocytes were found in the bone marrow. Cytogenetic analysis revealed deletion of the long arm of chromosome 5 (5q-). Subsequently, hemoglobin and platelet counts decreased gradually, splenomegaly appeared and progressed, after which myelofibrosis developed. Acute leukemia developed 16 years after the first documentation of thrombocytosis. 5q- syndrome is known to be a myelodysplastic syndrome (MDS) with unique clinical features and cases with this syndrome presenting with thrombocytosis of more than 1,000 x 10(9)/L but without anemia are rare. Furthermore, it is noteworthy that in this patient transition to acute leukemia occurred following development of myelofibrosis and marked splenomegaly, which are generally observed in blastic crises resulting from chronic myeloproliferative disorders (CMPD). The patient showed features indicative of CMPD rather than of MDS in spite of presenting with 5q- chromosomal abnormality. This case supports the concept of "mixed myelodysplastic and myeloproliferative syndromes" and suggests the possibility of the appearance of CMPD-like manifestations in 5q- syndrome.

The effects of thrombopoietin (TPO) on cell proliferation and differentiation, and the relation between these effects and the expression of c-mpl on leukemia cells were studied in seven acute myelogeneous leukemia cell lines and seven myelogeneous blast cell preparations from patients with chronic myeloproliferative disorders (CMPDs) and myelodysplastic syndrome (MDS). Among the leukemia cells, five preparations of megakaryoblastic leukemia cells from patients and one megakaryoblastic cell line, CMK 11.5, proliferated in response to TPO in vitro. CMK 11.5 and the blastic cells from one patient diagnosed with MDS with myelofibrosis differentiated with increasing expression of CD41a in response to TPO. However, TPO had no effect on the cells lacking megakaryocytic characteristics. Some patients with CMPD and MDS develop acute transformation with blasts demonstrating megakaryocytic features, and some of these cells show growth in response to TPO. Therefore, in vivo administration of TPO should be considered carefully for patients with CMPD or MDS, since TPO may induce leukemic cell proliferation.

We have used the 7AAD/PY method to analyze the cell cycle status of normal human bone marrow hematopoiesis, and found that the cell kinetics differed. There were cells with relatively low levels of RNA in the S-phase (Type I) and a high level in the S-phase (Type 11). T-cells, B-cells, nucleated red cells and CD34+/CD19+ early B-cells in bone marrow were Type I, whereas myelomonocytic subset and CD34+/CD33-dim+ common myeloid cells were Type II. AC133+/CD38-dim cells, which were thought to be lineage-marker negative hematopoietic stem cells, had intermediate amounts of RNA in the S-phase between Type I and II (Type 0). Seventy-four cases of acute leukemia were also analyzed. Most of the T- and B-ALL cases were found to be Type I, most of the ANLL cases were Type II, and there were 10 cases that were Type 0. These findings yielded fundamental information about normal hematopoiesis and acute leukemia.

Background: No technique has been reported to analyze directly the antigen expression on basophil leukocytes when using a flow cytometer; therefore, the exact phenotype of human basophils and the character of the peroxidase in basophils are not well understood. Methods: Human blood basophils were purified by using an antibody against high-affinity Fc epsilon receptor (hFcϵR) and a MACS™ magnetic cell sorting system and then cytochemically stained. The phenotype and peroxidase of the human basophils were flow cytofluorometrically analyzed directly in unseparated blood and bone marrow samples as hFcϵR+/MBP+ (major basic protein)/Hist+ (histamine) light-density cells distributed in the high side-scatter area of lymphocytes on light scattergrams. Results: The peroxidase granules of human basophils were stained by an anti-eosinophil peroxidase (EPO) antobody. The human blood basophils had common granulocyte markers plus CD25, i.e., they were CD11a/CD11b/CD11c/CD25/CD38/CD13/CD33/hFcϵR/MBP/Hist/EPO positive, CD71 dim positive, CD14/CD15 partially positive, and CD2/CD3/CD7/CD122/CD16/CD56/CD57/CD10/CD19/CD20/CD22/HLA-DR/MPO (myeloperoxidase)/CD23 negative. Further examination was done to analyze the expression of colony-stimulating factor receptors on three lineages of granulocytes, i.e., basophils, eosinophils, and neutrophils. The neutrophils were CD114 (G-CSFR)/CD116 (GM-CSFR)/CD124 [interleukin (IL)-4R]/CD126 (IL-6R) positive and CD123 (IL-3R)/CD125 (IL-5R) negative. In contrast, the eosinophils and basophils were CD116/CD123/CD125/CD126 positive and CD114/CD124 negative. Conclusions: This novel technique for directly characterizing human basophil leukocytes with flow cytometry may be a convenient way to screen the expression of surface antigens and the cytoplasmic expression of CD antigens and other proteins in human blood basophils and to analyze alterations of the character of basophils by cytokines and other biological substances in vivo and in vitro. Cytometry 35:249–259, 1999. © 1999 Wiley-Liss, Inc.

Although peroxidase activity in basophils can be detected by optical and ultrastructural cytochemistry, its characteristics remain to be determined. We have demonstrated the characteristics of peroxidase activity induced in the immature basophil cell line, KU812-F. Ultrastructurally, peroxidase activity was detected in granules as well as in the perinuclear space and endoplasmic reticulum. Immunocytochemistry revealed that KU812-F cells were stained by anti-eosinophil peroxidase antibodies, and eosinophil peroxidase mRNA, not myeloperoxidase, was detected in the cells using Northern hybridization and reverse transcription-polymerase chain reaction. Eosinophil peroxidase can be one of the molecules shared with eosinophils and basophils. The biological function of eosinophil peroxidase detected in basophils remains uncertain.

Transient myeloproliferative disorder (TMD) in neonates with Down syndrome is characterized by increased megakaryoblastic cells in the peripheral blood. Despite their spontaneous regression in weeks, prognosis is not always favorable because of fatal hepatic fibrosis. In this study, blood thrombopoietin (TPO) levels were measured by ELISA in six TMD patients and the expression of c-Mpl, a ligand for TPO, was examined on the blast cells from four patients by flow cytometer. At the onset, TPO level was undetectable in one patient and significantly lower in five patients than six neonatal controls (mean 0.52 fmol/ml, range 0.30-0.93 vs. 3.70, 1.38-8.33, P < 0.001), although platelet counts were similar (mean 321 x 10(9)/l, range 42-1,040 vs. 253 x 10(9)/l, 124-381). Two patients died of hepatic failure. TPO levels were measured in five patients after regression of the blast cells. With regression of blast cells, TPO levels were remarkably increased in four survived patients. In one patient with hepatic failure, TPO level was poorly elevated and relatively lower compared to the others. TPO levels were inversely correlated with blast numbers (r = -0.85, P < 0.001), but not with platelet counts (r = 0.426). Blast cells from four patients were all positive for c-Mpl. Our findings suggest that megakaryocyte mass is a major regulator of TPO levels and hepatic failure may affect the TPO level because liver is a major source of TPO production.

We recently established a human granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell line (HML) from colony-constituent cells grown by peripheral blood cells of a patient with acute megakaryoblastic leukaemia. The HML cells possessed megakaryocytic features, as determined by cytochemical, electron microscopic and flow cytometric analysis. In the present study we examined the effects of retinoic acid (RA) on the development of HML cells. All-trans-RA, 13-cis-RA and 9-cis-RA at 10−8 mol/l to 10−5 mol/l inhibited the GM-CSF-dependent cell growth. Some of the RA-treated cells contained prominent azurophilic granules and were positive for peroxidase. They also reacted with Biebrich scarlet, Luxol fast blue and a monoclonal antibody against eosinophil peroxidase. In addition, exposure to RA increased the frequency and the intensity of major basic protein-positive cells. However, eosinophil-derived neurotoxin and eosinophil cationic protein were not detected or were only detected at a low level in the lysates of the HML cells treated with RA. Although IL-5 alone could not stimulate cell growth, the addition of IL-5 to the cultures containing stem cell factor + all-trans-RA was required for the expression of the eosinophilic phenotype. These results suggest that the HML cell line is a megakaryoblastic cell line with the potential to differentiate into the eosinophilic lineage. HML cells may be a useful model for elucidating the eosinophilic differentiation programme.

In normal hematopoiesis, stem cell factor (SCF) stimulates survival, proliferation and differentiation of hematopoietic progenitors. Although SCF acts synergistically with a variety of cytokines, the mechanism of growth factor-cooperation remains to be determined. To analyze the synergism between SCF and granulocyte-macrophage colony-stimulating factor (GM-CSF), we established a new megakaryoblastic cell line, HML-2, by culture in the presence of both SCF and GM-CSF. While SCF alone or GM-CSF alone supported modest cell growth, SCF and GM-CSF together induced substantial growth of this cell line. SCF alone tyrosine-phosphorylated several bands including the 145 kDa subunit of c-kit. GM-CSF alone did not cause the tyrosine phosphorylation of the 145 kDa subunit, but markedly up-regulated the expression of the 145 kDa subunit of c-kit. The combination of SCF and GM-CSF resulted in a synergistic increase in tyrosine phosphorylation of the 145 kDa subunit of c-kit. Several proliferation inhibitors which removed the two-factor interaction on the growth of the HML-2 cells down-regulated the 145 kDa subunit of c-kit. Thus, a synergistic increase in tyrosine phosphorylation of the 145 kDa subunit of c-kit may be one possible mechanism underlying the cooperation of SCF and GM-CSF on the HML-2 cell growth.

A patient presented with chronic large granular lymphocyte leukemia associated with chronic active Epstein-Barr virus infection (CAEBV). Cell cycle analysis revealed a minimal growth compatible with chronic lymphocytic leukemia After 5 months of treatment, the patient died from acute transformation of the leukemia. Cell harvested during chronic phase were analyzed for sensitivity to interleukin 2 (IL-2) and interferon alpha (IFN alpha) in vitro by means of surface phenotyping and cell cycle assay. IL-2 induced remarkable growth of the cells, whereas IFN alpha did not confer a growth advantage. Since IFN alpha was expected to have no growth induction effect on the leukemia cells, it was administered to the patient to treat the CAEBV.

Primary familial and congenital polycythaemia (PFCP) is a rare disease characterized by congenital erythrocytosis inherited in an autosomal dominant fashion. Recently, mutations in the erythropoietin receptor (EpoR) have been identified in PFCP families. We describe a Japanese family with an autosomal dominant inheritance of PFCP. An in vitro colony assay demonstrated hypersensitivity of erythroid progenitors to erythropoietin (Epo) in affected family members. Sequence analysis of RT-PCR products amplified from the C-terminal region of EpoR transcripts in affected family members revealed that they were all heterozygous for C and T bases at position 5986, which suggested a genetic mutation (C to T) on one allele of EpoR. This mutation gave rise to a translation termination codon TAG at amino acid 435. Thus, the resulting EpoR is a truncated protein product lacking all 74 amino acids downstream of the mutation. To date, all genetic mutations affecting a family with PFCP, including this one, have been located in the cytoplasmic negative regulatory region of the EpoR. All mutations gave rise to truncated Epo receptors between Tyrosine 427 and Tyrosine 455. The phosphotyrosines in this region of EpoR have been demonstrated to be binding sites for SHP-1 phosphatase. Therefore PFCP is presumably brought about as a result of genetic mutations which cause the loss of the SHP-1 binding site in the cytoplasmic region of EpoR.

Several means of analyzing minimal residual disease (MRD) in leukemia involving the rearranged T cell receptor (TCR) gene have been described. We investigated MRD in leukemia with TCR beta rearrangement by examining TCR beta-chain RNA. A complementary DNA (cDNA) corresponding to the variable region of the TCR beta-chains originating from the peripheral blood or bone marrow from four patients was amplified. Single strand conformation polymorphism (SSCP) analysis of amplified cDNA showed that all four patients had monoclonal leukemia with TCR beta rearrangement; two patients had Vbeta2+ leukemia, another patient had Vbeta14+ leukemia and the other had Vbeta9+ leukemia. Flow cytometry supported this finding. Sequencing of the Vbeta2-complementarity determining region 3 (CDR3), Vbeta9-CDR3 and Vbeta14-CDR3 revealed monoclonality. To investigate MRD using TCR beta-chain RNA, cDNA from each patient was diluted with the cDNA of a healthy person and amplified using a specific CDR3 clonotype primer. A band in the ethidium bromide-stained agarose gel was detected from samples diluted 10,000-fold. SSCP analysis determined which V region gene was utilized in monoclonal leukemic cells. The leukemic cell specific TCR, determined in such a manner, may be a target for immunotherapy. Because the MRD of T cell malignancy can be easily examined once the CDR3 clonotype primer is made, this novel analysis is considered to be a useful method.

Ten patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). Eight of 10 patients achieved complete remission (CR), and among the 8 newly diagnosed cases, 7 achieved CR. Five of 8 CR cases remained in CR after 8 to 30 months. Except for hypotension and a large gastric ulcer resulting from hyperhistaminemia, the adverse effects of ATRA were generally mild. Severe thrombotic tendency occurred in a patient treated with ATRA combined with tranexamic acid. Intensive chemotherapy consisting of daunorubicin (DNR) and other agents was scheduled for the patients who achieved CR with ATRA.

We developed an improved technique that permits simultaneous DNA and RNA quantitation by a flow cytofluorometry using 7-amino-actinomycin D (7AAD) and pyronin Y (PY), respectively. Detailed cell cycle analyses based upon the cellular DNA/RNA levels were performed using cells suspended in a buffer containing 0.004% saponin. This method preserved the light scattering properties of human peripheral blood cells, thus lymphocyte, monocyte and granulocyte populations could be evaluated. In addition, since 7AAD and PY exhibit red (> 650 nm) and orange fluorescence (570 nm) respectively, the green fluorescence channel of the flow cytometer was reserved for surface phenotyping using FITC-conjugated antibodies. The 7AAD/PY method is applicable to the simultaneous three-color analysis of the surface phenotype and DNA-RNA quantitation when combined with FITC-conjugated surface markers in heterogeneous samples. To demonstrate the three-color analysis, PHA-activated human peripheral blood lymphocytes were stained for cell surface markers with monoclonal antibodies. The cells were suspended in buffer containing 0.004% saponin, then stained with 7AAD and PY. The DNA and RNA were analyzed in indivisual CD4+, CD8+ and CD20+ cells, and the characteristic cell cycle status was found. Cell activation was further analyzed using antibodies against interleukin-2 (IL-2) receptors (CD25), transferrin receptors (CD71) or HLA-DR molecules. Transferrin receptors were expressed in late G1 phase (G1B) just before the initiation of DNA synthesis, whereas IL-2 receptors and HLA-DR were expressed very early in the G1 phase (G1T). Since this technique preserves both light scatter properties as well as cell surface proteins, it is ideally suited for detailed cell cycle analyses of heterogeneous samples such as peripheral blood or bone marrow cells.

We report a 54-year-old man with acute myeloid leukemia (AML) carrying del(7)(q32) and inv(16)(p13q22). He was diagnosed as having AML M4Eo according to the FAB classification. RT-PCR for CBFβ/MYH11 gene was positive. Karyotype analysis revealed the primary chromosomal abnormality to be del(7)(q32) and inv(16)(p13q22) developed as a secondary abnormality. He achieved complete remission after one course of induction chemotherapy and remained in remission after several courses of consolidation therapy. del(7q) is classified into an intermediate risk group or an adverse risk group, while inv(16)/t(16;16) is classified into a favorable risk group. Some AML cases with inv(16)/t(16;16) exhibit del(7q) as an additional chromosomal abnormality. It was reported that such cases showed good prognosis despite the presence of del(7q). However, AML cases with del(7q) and inv(16)/t(16;16) as secondary chromosomal abnormalities are rare. Further study is needed to clarify the clinical manifestations of such cases.

A 63-year-old man had repeated melena of unknown origin from March 10, 1991. On February 7 1992, the patient developed melena followed by abdominal pain in the early morning and was referred to the hospital for admission. There were tenderness with muscular defence and Blumberg sign in the abdomen. Simple X-ray examination of the chest and abdomen showed free air under the diaphragm. From these findings the patient was diagnosed as having a gastrointestinal perforation. Laparotomy was immediately performed and a diverticulum with a perforation 8mm in diameter in the jejunum at 2mm anal side from the Treitz ligament was found. The diverticulum was 8cm in size, was located on the antimesenteric side, and a hard tumor mass with the size of tip of the finger was palpated in a part of the wall. Partial excision of the jejunum including the diverticulum was performed. This case was of true diverticulum of the jejunum associating with an extramural lyomiosarcoma in which tumor cells invaded almost entire the diverticulum and the perforation was formed in its ulcerated part. In this paper a rare case of jejunal diverticulum with a leiomyosarcoma in which hemorrhage was repeated from erosion and ulcer in the lumen probably forming a perforation is described.

A 77-year-old man was admitted to the hospital because of hematemesis which followed epigastric discomfort on the day before (March 30 1992). There was a history of undergoing gastrectomy with B-II reconstruction for gastroduodenal ulcer at the age of 40. On admission emergency endoscopy of the stomach revealed a giant submucosal tumor occupying almost entire the lumen of the remnant stomach, however, no bleeding source was detected. Blood transfusion was started, but the patient was transferred to the department of surgery of Showa University on April 19, because his blood showed irregular antibody positive and transfusional blood supply was difficult. Leiomyosarcoma of the remnant stomach was suspected and laparotomy was carried out on April 15, when a 15cm submucosal tumor with an ulcer on the top was found. Total excision of the remnant stomach was performed. Histopathologically it was diagnosed as leiomyosarcoma. This paper presents a rare case of giant leiomyosarcoma of the remnant stomach of lumen type.

A 49-year-old man was seen at the hospital, because of occult blood of stool in June 1990. Based on barium enema and colonoscopy findings, the diagnosed as colonic polyposis. Biopsy at colonoscopy resulted in Group 1-2. For subsequent 3 years the clinical course was followed by barium enema and colonoscopy, but no significant change was observed. In December 1992 polypectomy was done at colonoscopy and carcinoma in adenoma was detected in 4 out of 11 polyps. Operation comprising colectomy, ileorectal anastomosis, and J. pouch was carried out. In the excised specimen 134 polyps were found. This paper presents a case of colonic polyposis, in which clinical course was followed for 3 years, and synchronous multiple carcinomas changed from polyps were successfully resected on an appropriate timing in terms of social and physical conditions of the patient.

Sodium selenocarboxylates were found to react with organoarsanyl chlorides Ph 3-n AsCl n 1-3 (n=1, 2, 3) to give the corresponding Se-organoarsanyl esters RCOSeAsPh 2 (5), (RCOSe) 2 AsPh (6) and (RCOSe) 3 As (7) in good yields. The reaction of Se-dipbenylarsanyl 4-methylbenzenecarboselenoate 5g with phenylselenenyl bromide and phenyltellurenyl iodide afforded the corresponding 5e-phenylselenenyl 13 and Se-phenyltellurenyl esters 14 in moderate yields, while the reaction with sodium phenoxide gave sodium 4-methylbenzenecarboselenoate (4g), phenyl 4-methylbenzoate (11) and phenoxydiphenylarsine (12), indicating the attack of phenoxy anion to both the carbonyl carbon and arsenic atoms

Aseptic abscesses syndrome (AA) is an emerging clinicopathological entity characterized by visceral sterile collections of mature neutrophils that do not respond to antibiotics but regress quickly when treated with corticosteroids. Although most previous case reports of AA have been restricted to Europe, we present here a Japanese woman with AA showing recurrence of splenic abscesses, ileocolitis, pyoderma gangrenosum, and arthritis. Although both steroid therapy and tumor necrosis factor (TNF)-alpha blockade were effective, relapses remained frequent.

Epstein-Barr virus (EBV)–DNA was prospectively analyzed in plasma and mononuclear cells (MNCs) from peripheral blood in patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, to evaluate the clinical significance for diagnosis, monitoring the tumor burden, and prognostication. Thirty-three patients were enrolled, and 32 were evaluable. Pretreatment plasma and MNC EBV-DNA was detectable in 14 (range, 50-71 000 copies/mL) and 6 patients (range, 20-780 copies/μg DNA), respectively, and both were well correlated (r = 0.8741, P < .0001). Detectable plasma EBV-DNA was associated with higher clinical stage (P = .02), presence of B symptoms (P = .02), worse performance status (P = .02), and higher serum soluble IL-2 receptor level (P < .0001). Twenty-two patients attained complete response. Plasma EBV-DNA level was significantly higher in nonresponders than in responders (mean, 16 472 vs 2 645 copies/mL; P = .02). Multivariate analysis showed clinical stage (hazard ratio, 9.0; 95% confidence interval, 1.8%-45.0%) and pretreatment plasma EBV-DNA (hazard ratio, 10.6; 95% confidence interval, 1.3%-87.0%) were significant prognostic factors. Three-year overall survival of plasma EBV-DNA positive and negative patients was 42.9% and 94.4%, respectively (P = .0009). Plasma was a preferable sample for this purpose in NK/T-cell lymphoma, nasal type, and EBV-DNA level was a good indicator for response and overall survival.

IgG4-related disease is a recently recognized group characterized by elevated serum IgG4 levels and prominent lymphoplasmacytic infiltration of IgG4-positive cells into multiple organs (1). The condition was first described in relation to the pancreas (i.e., autoimmune pancreatitis [AIP] [2]), but since then many other inflammatory conditions associated with IgG4-related disease have been reported, including sclerosing cholangitis, sialadenitis, lymphadenopathy, retroperitoneal fibrosis, interstitial pneumonia, and tubulointerstitial nephritis (1,3,4). Laboratory findings in IgG4-related disease are commonly characterized by hypergammaglobulinemia and high levels of serum IgG and IgG4, and in addition, a high serum IgE level, peripheral eosinophilia, and hypocomplementemia are often observed (3,4). Thrombocytopenia in IgG4-related disease is rare, but a few cases of autoimmune thrombocytopenia have been reported in patients with AIP (5,6). We describe here, to our knowledge, the first case of acquired thrombotic thrombocytopenic purpura (TTP) in a patient with IgG4-related lung disease with severe deficiency of ADAMTS-13 activity and IgG4 autoantibody against ADAMTS-13.

1980年から1989年までの10年間に教室で経験した単発結腸癌治癒切除例210例中,術後吻合部再発をきたし,再切除を行ったのは3例(1.4%)である.初回切除標本の腫瘍占居部位は全例S状結腸であり,AWは5～10cmであった.全例壁深達度はs,リンパ節はn1(+)であり,ly因子はly2-ly3であった.再切除標本では,壁深達度は2例がsで,1例がpm,リンパ節転移は1例にみられたが,ly因子はly0-ly1と軽度であった.結腸癌術後吻合部再発の成因として,ly因子の他にimplantationの関与があるが,これらを文献的に考察した.

症例は,70歳,女性.1990年2月ごろよりの下血を主訴に同年5月15日当科初診す.肛門指診にて肛門縁より約3cm,6時方向に硬い腫瘤を触知し,注腸X線検査,大腸内視鏡検査にて2型の肛門管癌と診断,手術を施行したところ,病理検査所見はsquamous cell carcinoma pm n2(+)ly2 v0であった.また新鮮摘出標本の分子生物学的検査所見としてHPV-DNAアッセイ(HPV 6, 11, 16, 18, 31, 33, 35)が陽性であった.近年,HPV感染と悪性病変との関係が示唆され,なかでも肛門管癌とHPV感染の関係は,肛門管癌において肛門性交の既往のある男性同性愛者がhigh risk groupであると報告されて以来,とくに欧米において注目きれ,両者の関係を研究していくことが肛門管の発癌機構解明,ひいては発癌防止のためにも必要と考えられる.今回われわれは,文献検索上未だ本邦にて報告のないHPV感染を伴った肛門管癌の1例を経験したので報告する.

1981年から1991年までに教室で経験した大腸癌手術症例620例にみられた他臓器重複癌は34例(5.5%)であった.同時性重複癌は20例,異時性重複癌は14例であり,後者のうち,大腸癌先行は4例,他臓器癌先行は10例であった.重複癌の臨床病理学的特徴を明らかにする目的で,同時期の単発大腸癌症例512例を対照として比較検討したが,重複癌と単発癌との間で性別,年齢,占居部位,進行度に有意の差は認められなかった.重複癌の癌家族歴も高頻度ではなかった,予後は,重複癌でもともに治癒切除できた症例は良好であった.大腸重複癌の早期発見には,重複癌臓器として頻度の高い胃,子宮,乳腺の術前術後の検索が大切であり,子宮癌に対する放射線治療後の直腸癌発生にも留意する必要があると思われた.

当教室において過去9年間に経験した大腸癌は手術例468例であり,そのうち緊急手術を施行した68例(14.5%)について検討した.緊急手術例は非緊急手術例に比べ,stage Vの進行例が多く,切除率は低かったが(77.9%),治癒切除率および治癒切除例5年生存率は両者に有意差は認めなかった(p

Seeding metastasis of the hepatocellular carcinoma on the omentum is relatively rare (2-6%). Moreover, the rupture of the seeding metastatic hepatocellular carcinoma has not been reported so far.: A 46-year-old male, who had received the laparotomic hemostasis due to the rupture of hepatocellular carcinoma at one year before, was admitted with a lower abdominal pain. Physical findings on admission were supposed to being like a hypovolemic shock. The abdominal findings included bulging with fluctation and diffuse tenderness of the lower abdomen. Blumberg sign was noted. An about 10cm movable tumor was palpated in the right lower abdomen. Abdominal CT indicated intraperitoneal bleeding due to ruptured metastatic tumor of the small intestine, and an emergency operation was performed. The operative findings showed about 1300ml of blood collection in the peritoneal cavity and a 12×10cm metastatic tumor mass on the omentum, which was removed in the meantime. The patient was fine in the postoperative course.: This case report would be a first ruptured metastatic hepatocellular cartinoma on the omentum which may be seeded at the former intraperitoneal hemorrhage.

Acylselenenyl halides 2(X = Cl, Br) have been generated from RC(O)SeAsPh21 and N-halogenosuccinimide, and the chlorides 2(X = Cl) have been treated with enol silyl ethers to give Se-β-oxoalkyl Selenoesters 5 in good yields.

Our previous study demonstrated the positive relationship between the gene introduction rate into hematopoietic cell lines by electroporation and the percentage of cells in S-phase. In the present study, granulocyte-macrophage progenitor cells (CFU-C) rich marrow cell fraction were cultured in suspension with IL-3, GM-CSF and G-CSF for 4 days. The number of CFU-C were increased three times after the culture, and 3H-thymidine suicide tests of cultured cells demonstrated that the proportion of CFU-C in S-phase was increased by two to four times. The efficiency of gene transfer into CFU-C with the plasmid pMoZtk (containing the beta-galactosidase gene) by electroporation was nearly doubled by culturing marrow cells with these growth factors. These findings confirm that the introduction rate of the gene into CFU-C by electroporation is more efficient in cell populations with a higher percentage of CFU-C in S-phase.