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Hemophagocytic syndrome (HPS) is an unusual disorder associated with systemic lupus erythematosus (SLE). A 64-year-old woman was admitted because of fever and urticarial vasculitis. Laboratory data revealed pancytopenia and immunological abnormalities, suggesting elevated disease activity. Prednisolone monotherapy failed to improve the pancytopenia despite the amelioration of other clinical findings. Because her condition was suggestive of HPS, tacrolimus at 2-3 mg/day was added to the prednisolone regimen. Eventually, the pancytopenia improved and prednisolone could be effectively tapered. Tacrolimus could be an additional or alternative modality for treating refractory HPS.

We report a 73-year-old Japanese man with early onset pure red cell aplasia (PRCA) caused by subcutaneous administration of recombinant epoetin-β. Two months after the start of epoetin therapy, he developed PRCA. Anti-erythropoietin (EPO) antibody, detected in the patient's serum by enzyme immunoassay and radioimmunoprecipitation method, inhibited EPO-dependent growth of AS-E2 cells in vitro. Treatment with prednisone (1 mg/kg) significantly reduced antibody levels 3 months later. It is important to have an awareness of antibody-mediated PRCA. Our case shows that subcutaneous epoetin administration produces this complication in the early period of therapy.

A 74-year-old man presented with anemia, thrombocytopenia and leukocytosis with 41% abnormal cells having cleaved and monocytoid nuclei. The bone marrow was infiltrated with 43.6% abnormal cells that were negative for peroxidase staining and positive for PAS staining. Surface antigen analysis revealed no expression of CDs 2, 3, 4, 8, 10, 19, 20, 13 or 33. Serum immunoelectrophoresis detected a monoclonal band, which was identifiable as kappa-type IgA protein. Immunostaining also revealed expression of IgA and kappa-type in the abnormal cells. The patient was diagnosed as having plasma cell leukemia but the morphological findings were unusual. Surface antigen analysis revealed expression of CD38 later. This case suggests that immunostaining of abnormal cells is required for the differential diagnosis of plasma cell leukemia in leukocytosis.

Vitamin K2 is reported to induce apoptosis or differentiation of leukemic cell lines in vitro. We administered a vitamin K2 analog, menatetrenone, at 45 mg daily to 23 patients with myelodysplastic syndrome (MDS): 13 patients with RA, 2 with RARS, 6 with RAEB and 2 with RAEB-T. Good response (GR) and partial response (PR) were defined as an increase of hemoglobin concentration exceeding 2 g/dl and 1-2 g/dl without transfusion, respectively. Six of the RA patients showed improvement of anemia (GR, 3 patients; PR, 3 patients). RA patients who did not have a hypocellular bone marrow and were transfusion-independent tended to be responsive to vitamin K2 therapy in combination with vitamin D3 or anabolic steroids. No adverse effect of vitamin K2 was observed, and the time required to obtain the hematological response was short, being 3 months on average. We believe that vitamin K2 therapy has potential as a treatment for patients with MDS.

t(11:8) is a recurrent chromosomal abnormality observed in mucosa-associated lymphoid tissue (MALT)-type lymphoma. API2 and MLT genes have been implicated. The authors devised a dual-color interphase fluorescence in situ hybridization (FISH) system to detect splitting of 11q22 and its fusion with 18q21. Subjects were 44 cases of extranodal lymphoma and cases of primary macroglobulinemia. Whenever RNA was available, reverse transcriptase-polymerase chain reaction followed by sequence analysis was performed. Positive cases by dual-color FISH analysis were restricted to MALT-type lymphoma and one case of primary macroglobulinemia. Among 24 cases of MALT-type lymphoma, 14 (58%) (4 gastric, 5 pulmonary, 3 orbital, 1 salivary, and 1 thyroid lymphomas) had splitting of the 11q22 region probes and fusion of signals suggesting the translocation of chromosome 11 and 18. Reverse transcriptase-polymerase chain reaction analysis showed the API2/MLT gene fusion in 9 of 10 cases. Sequence analyses showed three different modes of involvement of the MLT gene, whereas the breakpoint at API2 was the same. Monoclonal component of serum immunoglobulin M was observed in 3 of 14 positive cases for the translocation. Direct visualization using dual-color FISH on samples serves as a molecular tool for management of MALT-type lymphoma with API2/MLT gene fusion.

A 16-year-old female patient was evaluated for pancytopenia. She had a white blood cell count of 1.6 x 10(9)/L with 0.02 neutrophils and a platelet count of 19 x 10(9)/L. In the bone marrow, mature granulocytes were markedly decreased in number, but no atypical cells were present. Antineutrophil antibody was demonstrated by flow cytometry, and the level of platelet-associated immunoglobulin G was increased. A diagnosis of autoimmune neutropenia and thrombocytopenia was made. Interestingly, neutrophil and platelet counts fluctuated cyclically after the initiation of prednisolone therapy. The neutrophil count fluctuated between 0.1 x 10(9)/L and 7 x 10(9)/L, and the platelet count fluctuated between 19 x 10(9)/L and 175 x 10(9)/L, in 4-week cycles. Following splenectomy, neutrophil and platelet counts normalized. We believe the immune mechanism of recurrent neutropenia in this patient differs from that in other patients with cyclic neutropenia reported with stem cell disorders.

We describe a rare case of cytotoxic gastrointestinal T-cell lymphoma with protein-losing enteropathy. Initial examination revealed the coexistence of T-cell lymphoma and tuberculosis in the mesenteric lymph node and liver. Despite anti-tuberculosis and anti-cancer treatment, the patient experienced chronic diarrhea and malabsorption and died approximately 3 years after onset. Autopsy specimens revealed medium-sized lymphoma cells, with a phenotype of CD3+, CD4-, CD7+, CD8+, CD30-, CD56-, CD103 (HML-1)-, TIA-1+, and granzyme B+, proliferating primarily and consistently in the mucosa of the entire bowel tract from esophagus to rectum. Interestingly, Epstein-Barr virus (EBV)-encoded small nuclear RNAs were detected in the tumors by in situ hybridization. Southern blot analysis revealed monoclonal proliferation in the EBV-infected T cells. Although the present case can possibly be categorized as an intestinal T-cell lymphoma according to the Revised European-American Lymphoma Classification, the case showed a unique clinical course and distribution of lymphoma cells. We present here an interesting case of gastrointestinal cytotoxic T-cell lymphoma and examine the possible association with infectious agents.

A 75-year-old woman presenting with myelodysplastic syndrome showed cyclic oscillations in her white blood cell and platelet counts. Each cycle lasted for 5 to 6 months, with 4 cycles occurring over the course of a 2-year period. During successive cycles, the white blood cell count fluctuated from 10.1 to 2.6; 13.8 to 1.8; 11.0 to 1.6, and 8.6 to 1.3 x 10(9)/L. The platelet count fluctuated from 242 to 38, 199 to 11, 110 to 5, and 75 to 3 x 10(9)/L. The patient underwent red blood cell transfusions because of red blood cell aplasia; the frequency of the transfusions and the erythropoietin concentration in serum were inversely correlated. The number of circulating granulocyte-macrophage colony-forming units and CD34-positive cells in peripheral blood oscillated in phase with the white blood cell and platelet counts. These patterns suggested a periodic influx of progenitor cells from hematopoietic stem cells. The ratio of neutrophils to mononuclear cells remained essentially constant throughout the clinical course. Lymphocyte subset assessments using monoclonal antibodies showed an inverse CD4/CD8 ratio (less than 1) and extreme B cell lymphopenia throughout the fourth cycle. The percentage of CD3-positive cells oscillated inversely, suggesting that the cyclic cytopenia had an immune mechanism involving T lymphocytes.

Thiazolidinedione (TZD) is known to be a potent activator of peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor that constitutes a heterodimer with retinoid X receptor (RXR). Since a considerable amount of PPARgamma is expressed in various hematopoietic cells, the present study was undertaken to examine the effect of TZD in the absence or presence of LG100268, an RXR-selective ligand, on a cultured promyelocytic leukemia cell line, HL60. Treatment with TZD (25-50 microM troglitazone or pioglitazone) markedly suppressed cell proliferation of HL60. A cell cycle analysis revealed that the suppressive effect of troglitazone on HL60 cell proliferations was caused by G0/G1 cell cycle arrest as well as by an apoptotic effect. Treatment with the same concentration of troglitazone also induced the monocytic differentiation of HL60 cells. The apoptotic or the differentiating effect of TZD on HL60 cells was synergistically enhanced by the combined treatment with 1 microM LG100268, while LG100268 alone neither had an apoptotic nor a differentiating effect on HL60 cells. These results suggest that these actions are mediated through the nuclear receptor system constituted by the PPARgamma: RXR heterodimer.

Because retinyl palmitate was reported to be more stable to oxidation than retinol, we wondered if retinyl palmitate was also more resistant to photolysis as compared to free alcohol. We investigated the resistance of ethanolic solutions of retinol, retinyl palmitate, or both to air oxidation and (or) photolysis using fluorescent light. The initial concentrations were all-trans-retinol, 14 mumol/L, and all-trans-retinyl palmitate, 14 mumol/L. The concentrations of retinol and retinyl palmitate were determined by HPLC and are expressed as a percentage of their original concentrations. After 4 h of exposure to an 18 W fluorescent lamp at 15 cm from the solution, the means (SD) of the surviving analytes were 64% (3%) for retinol and 5% (2%) for retinyl palmitate in a solution containing both retinol and retinyl palmitate. Taking account of the cis isomer arising from retinyl palmitate, 29% (3%) of the retinyl palmitate survived after 4 h of photolysis. Degradation of retinyl palmitate might occur after the conversion of trans isomer to cis isomer during photolysis, however, trans isomer could be degraded with a lesser extent of isomerization. After 4 h of bubbling air through the solution in the dark, 49% (6%) of retinol and 69% (4%) of retinyl palmitate survived. Exposing retinol or retinyl palmitate separately to air oxidation, bubbling air through the solution, or photolysis, exposing them to light, we found that retinyl palmitate could retard the air oxidation of retinol (p < 0.001), but it had no effect on the light-induced degradation of retinol. We also studied the effect of the addition of approximately 1,560 mumol/L alpha-tocopherol, approximately 190 mumol/L beta-carotene and approximately 2,000 mumol/L ascorbic acid as antioxidants. In the presence of 156 mumol/L alpha-tocopherol, 87% (1%) of the retinol and 91% (4%) of the retinyl palmitate remained after air oxidation. Although the photolysis of retinol and retinyl palmitate was also inhibited by 190 mumol/L beta-carotene, alpha-tocopherol and ascorbic acid did not exert inhibiting effects. We conclude that retinyl palmitate is physico-chemically more labile to photolysis but is more resistant to air oxidation than retinol.

The soluble form of Fas (sFas) can block apoptosis induced by the Fas ligand in vitro. A recent report demonstrated that mice injected with sFas displayed autoimmune features. Therefore, an elevated serum concentration of sFas may be associated with lymphoproliferation and autoimmune diseases. We measured the serum concentrations of sFas in 77 patients with non-Hodgkin's lymphoma (NHL) [8 angioimmunoblastic T-cell lymphoma (AIL), 12 T-cell NHL, 53 B-cell NHL, and 4 natural killer-cell NHL]. Elevated concentrations of sFas were detected only in AIL, which is frequently accompanied by autoimmune diseases (P < 0.005 compared with age-matched controls). A possible association of sFas and autoimmune features in AIL is discussed.

This is the first case of primary macroglobulinemia with t(11;18) (q21;q21) reported in the literature. A 77-year-old man was admitted to a hospital in December, 1994, with acute renal failure and pleural effusion. He was treated with prednisolone pulse therapy and his symptoms improved. He was referred to our hospital for further examination. Analysis of blood chemistry revealed macroglobulinemia (IgM-kappa). There were no other findings that would indicate a diagnosis of malignant lymphoma. A complete blood count revealed a hemoglobin level of 8.7 g/dl and a white blood cell count of 5,300/microliters with 11% abnormal lymphoid cells. Immunologic and karyotype analyses revealed that these abnormal cells were positive for IgM-kappa, CD19, and CD20, negative for CD5, and CD10, and had t(11;18) (q21;q21). The bone marrow had also been infiltrated by 8.6% abnormal lymphoid cells. Six other cases with t(11;18) (q21;q21) have been reported including 5 of small lymphocytic lymphoma and 1 of mucosa-associated lymphoid tissue-type lymphoma. The tumor cells in these cases were the same as in our case. Therefore, our report is in agreement with the finding that t(11;18) (q21;q21) might be one of the characteristic chromosomal abnormalities in mature B-lymphoid neoplasms.

We present a patient who developed severe anemia and neutropenia after receiving parenteral nutrition for 2.5 years. The serum levels of copper and ceruloplasmin were low, and the bone marrow showed the presence of ringed sideroblasts and vacuolated immature cells. The administration of copper chloride by bolus injection led to a rapid improvement in anemia and neutropenia. The number of progenitor cells (colony-forming unit-granulocyte-macrophage and erythrocyte) present before the copper supplementation was well preserved. It is therefore suggested that copper enzymes play an important role in the maturation of hematopoietic cells.