[A case of polyarteritis nodosa limited to both calves with a low titer of MPO-ANCA].

A-57-year-old woman had suffered from high fever, general malaise, and loss of weight (6 kg) since January, 2000. She was admitted to our hospital in May, 2000, because of gait disturbance following to swelling of bilateral calves with severe pain beside the above symptoms. Laboratory data showed leukocytosis (WBC 10,000/microliter), high ESR (98 mm/hr), positive CRP (3.43 mg/dl), positive ANA (x160), high titer of RA (266 IU/l), and a low titer of MPO-ANCA (18 EU). T 2-weighted magnetic resonance image (MRI) showed intensity area of the M. gastrocnemius. Skin biopsy specimens of the right leg demonstrated necrotizing arteritis of small-sized arteries. These findings supported the diagnosis of limited type of polyarteritis nodosa (PN). In this report, we demonstrate a rare case of PN limited to both calves with characteristic MRI findings and a low titer of MPO-ANCA.

[Two cases of cardiac aspergillosis with initial onset of arrhythmia during therapy of acute leukemia].

We have reported two women, aged 86 and 84 years, with cardiac aspergillosis with initial onset of arrhythmia during chemotherapy of acute myeloblastic leukemia and primary plasma cell leukemia, respectively. In leukopenia followed by chemotherapy, they suddenly had arrhythmias with high fever. The former had cardiac infarction with complete atrioventricular block and the latter was also cardiac infarction following to atrial fibrillation. In both cases, cardiac aspergillosis was not diagnosed by echocardigraphy but by autopsy. Since cardiac aspergillosis dose not have characteristic features clinically or examinationally, we need to consider arrhythmias revealed in leukopenia as one symptom of cardiac aspergillosis.

[Subcutaneous panniculitic T-cell lymphoma with chromosomal abnormalities and large granular lymphocytes morphology].

A 72-year-old woman was admitted because of a subcutaneous hip tumor. A biopsy specimen of the tumor showed a mixture of medium-sized and large lymphocytes infiltrating the subcutaneous fat tissue with a lobular panniculitis-like pattern--a histologic feature of subcutaneous panniculitic T-cell lymphoma (SPTCL). May-Grünwald-Giemsa-stained cytospin slides of freshly isolated neoplastic cell explants showed that the cells had the characteristics of large granular lymphocytes. Immunophenotypic analysis showed that the cells expressed CD56--a natural killer-associated antigen--as well as the cytotoxic T-cell phenotype CD3+ CD4- CD8+. Southern blot analysis revealed rearrangement bands of the TCR-beta chain gene. Chromosome analysis showed complex abnormalities including t(1;6) (q11; p21). The present case may shed some light on the origin and pathogenesis of SPTCL.

Abnormal immune function of hemopoietic cells from alymphoplasia (aly) mice, a natural strain with mutant NF-kappa B-inducing kinase.

Alymphoplasia (aly) mice, a natural strain with a mutant NF-kappa B-inducing kinase (NIK) gene, manifest a unique phenotype; they lack lymph nodes and Peyer's patches, have a disturbed spleen architecture, and exhibit defects in both Ab and cellular immune responses. Although a stromal defect caused by impaired lymphotoxin-beta receptor signaling accounts for their abnormal lymphoid organogenesis, the exact mechanisms underlying the development of immunodeficiency in aly mice are poorly understood. We therefore investigated the contribution of hemopoietic cells with the aly NIK mutation to the development of immunodeficiency. Transfer of aly/aly bone marrow cells into aly/+ mice resulted in poorly developed B cell follicles and lack of support for the development of germinal centers and isotype switching, indicating that the hemopoietic cells of aly mice contain an autonomous defect. However, follicular dendritic cell clusters were maintained in the spleens of these bone marrow chimeras, suggesting that the lack of follicular dendritic cell clusters in aly mice is probably due to the stromal defect. The aly mice lacked marginal zone B cells in their spleens, and aly/aly B cells showed an impaired proliferative response after in vitro stimulation. IL-2 production by activated T cells was also impaired. By contrast, the dendritic cells of aly mice exhibited grossly normal development and function. Supporting the concept of an autonomous cell defect, Rel protein expression was altered in aly/aly spleens. Thus, the aly NIK mutation affects hemopoietic cell function in an intrinsic fashion and, together with the stromal defect, may contribute to the development of immunodeficiency in aly mice.

Involvement of distinct cellular compartments in the abnormal lymphoid organogenesis in lymphotoxin-alpha-deficient mice and alymphoplasia (aly) mice defined by the chimeric analysis.

Both lymphotoxin-alpha (LTalpha)-deficient mice and alymphoplasia (aly) mice, a natural mutant strain, manifest a quite similar phenotype: lack of lymph nodes (LN) and Peyer's patches (PP), with disturbed spleen architecture. The mechanisms underlying the defective lymphoid organogenesis in these mice were investigated by generating aggregation chimeras; ex vivo fused morulae were implanted into pseudo-pregnant host females and allowed to develop to term. Chimeric mice between LTalpha-deficient mice and wild-type mice restored LN and PP almost completely, suggesting that LTalpha expressed by circulating bone marrow-derived cells is essential for lymphoid organogenesis as well as for organization of spleen architecture. By contrast, chimeric mice between aly mice and wild-type mice showed only limited restoration of LN and PP. This suggests that the putative aly gene product does not act as a circulating ligand for lymphoid organogenesis, like LTalpha. Rather, abnormal development of lymphoid organs in aly mice seems most likely due to the defective development of the incipient stromal cells of the LN and PP. Supporting this hypothesis, up-regulation of VCAM-1 on aly mouse embryonic fibroblasts by signals through LTbetaR, which is exclusively expressed by nonlymphoid cells, was disturbed. These studies demonstrate that LTalpha and the putative aly gene product together control lymphoid organogenesis with a close mechanistic relationship in their biochemical pathways through governing the distinct cellular compartments, the former acting as a circulating ligand and the latter as a LTbetaR-signaling molecule expressed by the stroma of the lymphoid organs.

[Plasma cell leukemia (IgA-lambda type) with polyclonal hypergammaglobulinemia].

An 84-year-old woman was admitted to Ehime University hospital because of fever and generalized swelling of lymph nodes. On admission, she did not have any bone diseases. The laboratory data included a WBC count of 60,900/microliter, with 80.5% atypical plasma cells in the peripheral blood and 26.4% in the bone marrow. The patient's serum total protein was 9.3 g/dl with increased polyclonal gamma-globulin (62.4%). Serum levels of LDH (1,986 IU/l) and IL-6 (34.3 pg/dl) were also elevated. Immunofixation-electrophoresis detected a monoclonal band defined as IgA-lambda type, with a broad band of polyclonal immunoglobulin. Southern blotting analysis demonstrated rearranged monoclonal bands in the JH and J lambda genes. Based on these findings, plasma cell leukemia (IgA-lambda type) was diagnosed. The patient was treated with combination chemotherapy for acute lymphocytic leukemia and achieved complete remission. However, she died of aspergillus sepsis two months after admission. After chemotherapy, the patients IgG and IgM levels normalized but IgA still showed a slight increase. IL-6 also decreased, from 34.3 pg/dl to 10.2 pg/dl. To our knowledge, this report is the first in the literature concerning a case of plasma cell leukemia with polyclonal hypergammaglobulinemia.

[Low titer cold agglutinin disease due to anti-HI antibody and a review of this disease in Japan].

A 79 year-old Japanese man was admitted because of brownish urine and Raynaud phenomenon. Laboratory data showed mild anemia with reticulocytosis, positive direct Coombs test against anti-C3, elevated level of lactate dehydrogenase, undetectable level of serum haptoglobin and low titer of cold agglutinin (1:256 at 4 degrees C), the immunoglobulin subclass of which was IgM. Cold agglutinin disease is usually associated with very high levels of cold agglutinins, the specificity of which is anti-I. This case had low titer cold agglutinin disease due to anti-HI cold agglutinin.

Ultrastructural study of the response of cells infected in vitro with causative agent of spotted fever group rickettsiosis in Japan.

The response of host cells L929 infected with causative agent of spotted fever group (SFG) rickettsiosis in Japan, the Katayama strain, was studied by electron microscopy. The rickettsiae penetrated the cytoplasm and multiplied here and after prolonged incubation progressed into the dilated cisternae of rough endoplasmic reticulum (rER), the perinuclear space, the deep invaginated nuclear membrane, and then the nucleoplasm of the host cells. The intranuclear rickettsiae showed different states: one type was enclosed by the double membrane of the host cell and the other type was free in the nucleoplasm. In addition to these double membrane-bound and membrane-free intranuclear rickettsiae, various membrane structures, including rER-like structures, were also found in the nucleus. The cells infected with the rickettsiae underwent distinctive morphological alterations which occurred mainly within intracellular membranes of the host cells. These findings indicate the possibility that the intracellular membranes are characteristic cytopathological sites in rickettsia-host cell interaction, and that these alterations may be related to a possible route of rickettsial penetration into the nucleus: passage through vesicles formed from invaginations in the nuclear membrane.

[Blast crisis of chronic myelogenous leukemia with blasts expressing both immature B lymphocyte- and myelomonocyte-associated antigens and differentiating into basophils in vitro].

A 43-year-old woman with Ph1-positive chronic myelogenous leukemia (CML) was diagnosed as having blastic crisis. The phenotype of blasts was CD9+, CD10+, CD19+, CD11b+ and CD33+, suggesting the B Lymphoid and myeloid mixed lineage. Two color analysis of CD10 and CD33 revealed that 50% of blast cells had both B lymphocyte- and myelomonocyte-associated surface markers. Rearrangement of the immunoglobulin heavy chain gene was detected. After culturing blasts with 12-o-tetradecanoyl-phorbol 13 acetate (TPA), basophilic granules appeared in cytoplasm of the cells. These granules were positive for toluidine blue staining. This finding that the biphenotypic blasts expressing both B lymphoid and myelomonocytoid features differentiated into basophils suggests that blasts of this case are derived from a common progenitor of B lymphoid and myeloid lineages including basophil.

Multiphenotypic lymphoma with rearrangements of the T cell receptor beta chain and gamma chain genes.

A case of chemotherapy-resistant non-Hodgkin's lymphoma simultaneously expressing T cell (CD7)-, B cell (CD19)- and myeloid (CD13, CD33)-associated surface antigens is presented. Cytochemical analysis revealed that the lymphoma cells were positive for terminal deoxynucleotidyl transferase, but negative for myeloperoxidase and esterase. Rearrangements of both the T cell receptor beta chain and gamma chain genes were observed, but the immunoglobulin genes showed a germ line configuration. The rearrangement was not detected within the breakpoint cluster region on chromosome 22. These findings are considered to represent aberrant expressions of the B cell- and myeloid-associated antigens in early-stage T cell lineage lymphoma cells.

A case of chronic myelogenous leukemia with T lymphoblastic and megakaryoblastic mixed crisis.

We report a case of blast crisis in chronic myelogenous leukemia (CML) in which T lymphocytic and megakaryocytic lineages were both involved. A 55-year-old male was initially admitted to Ehime University Hospital because of generalized lymphadenopathy. The morphological features of peripheral blood and bone marrow were consistent with chronic phase of CML. Cytogenetic studies of bone marrow and lymph node cells both showed the Ph1 chromosome with additional abnormalities. The patient was diagnosed as being in the extramedullary blast crisis of CML involving lymph nodes. After six months, blasts increased in bone marrow and peripheral blood. The phenotypes of lymph node blasts were positive for CD2, CD7 and TdT, but negative for CDw41 (platelet glycoprotein IIb/IIIa). On the other hand, those of peripheral blood blasts were positive for CDw41, but negative for CD2, CD7 and TdT. Chromosome studies of lymph node cells and bone marrow cells revealed 46, XY, inv(7) (p15q34), t(9;22) (q34;q11) and 46, XY, t(1;3) (q23:q21), t(9;22) (q34;q11), respectively. The rearrangement of T cell receptor beta chain gene was detected in lymph node blasts, but not in peripheral blood blasts. The identity of the rearrangement patterns of the breakpoint cluster region on chromosome 22 was detected in these blasts. According to these data, it was suggested that blast crisis of CML occurred in two distinct lineages, T lymphocyte and megakaryocyte.

Phenotypic and genotypic analysis of chronic myelogenous leukaemia with T lymphoblastic and megakaryoblastic mixed crisis.

A case of blast crisis in chronic myelogeneous leukaemia (CML) in which two distinct cell lineages were involved is presented. The phenotype of blasts in lymph nodes was T11 (CD2)+, Ia+, TdT+, suggesting T cell lineage. On the other hand, blasts in bone marrow and peripheral blood expressed platelet glycoprotein IIb/IIIa complex on their surface, suggesting megakaryocyte lineage. Cytogenetic analysis of lymph node and bone marrow cells revealed the abnormalities, inv(7) (p15q34) and t(1;3) (q23;q21), respectively, as well as the presence of the Ph1 chromosome in both cell types. Rearrangement of the T cell receptor beta-chain gene was detected in lymph node blasts, although blast cells in peripheral blood showed a germ line configuration. The involvement of T cell and megakaryocyte lineages in the blast crisis phase of CML was confirmed in our phenotypic and genotypic analysis, and the pathogenic association between blast crisis lineages and the additional chromosome abnormalities present is discussed.