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Background Reticulated platelets (RPs) as measured using flow cytometry are useful parameters of thrombopoiesis; however, difficulties remain with standardization between laboratories. On the other hand, immature platelet fraction (IPF) measurement, as determined using an automated hematology analyzer, is simple, reproducible, and displays a good correlation with RP, although specific factors may affect its value. We previously noticed that a small proportion of patients exhibit extremely high IPF values that do not correlate with flow cytometrically measured RP. Objectives We investigated the mechanism of the aberrant increase in IPF values of different types of macrothrombocytopenia. Patients/methods IPF, RP, and other platelet indexes were analyzed using samples from 15 congenital macrothrombocytopenic patients from 12 families, 150 immune thrombocytopenic patients, and 27 normal individuals. We further monitored the change in IPF values and morphology during platelet agglutination. Results IPF values were about five times higher in MYH9 disorders (IPF 48.6 ± 1.9%) and about twice as high in other macrothrombocytopenias (IPF 18.4 ± 2.1%) than in immune thrombocytopenic patients with similar platelet counts (IPF 9.2 ± 0.3%). We then examined changes in IPF values during ethylenediaminetetraacetic acid- and macroglobulinemia-induced platelet agglutination. The IPF value significantly increased in a time-dependent manner along with the formation of platelet clumps and was strongly influenced by a few tiny platelet aggregates. Conclusions These results suggested that IPF values are influenced by platelet size. Furthermore, IPF could be a useful and convenient parameter for screening of macrothrombocytopenia, which presents with a disproportionately high IPF value. [ABSTRACT FROM AUTHOR]

A quantitative imbalance between matrix metalloproteinases produced by cancer cells and tissue inhibitors of metalloproteinases produced by fibroblasts and other types of cells has been demonstrated to be a causative factor in invasion and metastasis of cancer cells. On the other hand, it is reported that sugar chains of adhesion molecules such as integrins and CD44 also influence the metastasis of cancer cells. Here, alterations of serum IgG oligosaccharide chain structure were investigated during tumor progression using the new method of fluorophore-assisted carbohydrate electrophoresis (FACE). The structure of serum IgG oligosaccharide chains from 22 cancer patients (11 localized cancer, 11 metastatic cancer) and 10 healthy controls was evaluated by FACE. It was clearly demonstrated that serum IgG oligosaccharide chains without galactose (agalactosyl IgG oligosaccharide) significantly increased with tumor progression of lung and gastric cancers. It is concluded that a marked increase of agalactosyl IgG oligosaccharide in these cancer patients is associated with carcinogenesis and metastasis. Therefore, the analysis of serum IgG oligosaccharide chain structure by FACE may be useful for evaluating diagnosis and prognosis in patients with these carcinomas. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Lenalidomide is now widely used for the treatment of multiple myeloma in virtue of its potent anti-tumor activity and low toxicity. Very few reports stressed the association of this drug with serious pulmonary toxicity. Here we present the case of multiple myeloma who underwent acute respiratory failure caused by non-specific interstitial pneumonia after few days of treatment with lenalidomide., Case Summary: A 50-year-old man diagnosed as multiple myeloma of IgA κ type, International Staging System III received a combination therapy of lenalidomide (15 mg, Day 1 - 21) with dexamethasone (40 mg, Day 1, 8, 15, 22). After 4 days on chemotherapy, he experienced worsened dyspnea and was urgently hospitalized because of acute respiratory failure. Because serial imaging procedures and thorough laboratory workup strongly suggested that his lung injury was caused by drug-induced interstitial pneumonia, lenalidomide, which was the most suspicious drug, was discontinued immediately, and the glucocorticoid pulse was performed. He showed an excellent response to the therapy. Interstitial pneumonia on the CT scan was resolved dramatically at 12 days after the start of the glucocorticoid pulse., Conclusion: We are convinced that our case is so instructive as to arouse attention to clinicians that lenalidomide has an extremely rare but potential adverse effect.

Acquired hemophilia (AHA) is a relatively rare and life-threatening disease caused by autoantibodies against factor VIII. Autoimmune bullous diseases (ABD) are also caused by autoantibodies against specific skin proteins. We herein report two cases of AHA associated with ABD. These coincidences are extremely rare, and only 14 documented cases have been reported previously. We further analyzed the properties of the autoantibodies in our patients. The epitopes were the A2 domain in patient 1, and both the A2 domain and the light chain in patient 2. Their isoforms were predominantly IgG4. Cross-reactivity could not be demonstrated. An accumulation of cases is required to unveil the pathogenesis of AHA.

CD3 is a complex of polypeptides which form part of the T cell receptor. Normal human peripheral pan T cells, express not only CD3, but the mRNA for myosin regulatory light chains MYL9, MYL12A, and MYL12B are also significantly expressed. In the Jurkat wild strain, an acute T cell leukemia cell line, CD3 on the surface and MYL9 mRNA are not expressed, while both MYL12A mRNA and MYL12B mRNA are expressed. Jurkat-I, a new clone was established by the transfection of the MYL9 gene into the Jurkat wild strain. As a result, the level of CD3 expressed on the surface of Jurkat-I cells was significantly higher than those in the Jurkat wild strain. Phorbol 12-myristate 13-acetate increased the surface CD3 levels in Jurkat wild strain cells without resulting in MYL9 gene expression, indicating that protein kinase C is partially involved in the expression of CD3 on the surface. These results suggest that surface CD3 expression proceeds through both MYL9-dependent and MYL9-independent pathways (i.e. the protein kinase C- dependent pathway) in Jurkat cells.

Constitutive activity of nuclear transcription factor kappaB (NF-kappaB) is observed in many pathological types of lymphoma that are associated with a poor clinical course. This suggests that NF-kappaB and pathways involving NF-kappaB are possible targets for successfully treating lymphoma. We examined 28 lymph nodes from 28 patients in whom follicular lymphoma was diagnosed from 1996 to 2006 at our institution, which were formalin-fixed and paraffin-embedded. The specimens were stained with an antibody that could recognize activated NF-kappaB and p65 to determine whether they were positive or negative for NF-kappaB activation. The clinical courses of the 28 patients were then correlated with the results of the NF-kappaB staining. The 10 men and 18 women had a mean age of 57.3 years (range, 25-87 years). By follicular lymphoma grade, 10 patients had grade 1, 16 had grade 2, and 2 had grade 3a. Ten patients died due to lymphoma. NF-kappaB was positive in 6 of the 28 cases. Analysis of the positive and negative staining groups while taking into account the clinical course, sex, age, grade of follicular lymphoma, prognostic index, CD10, CD23, Bcl-2, karyotype t(14;18), and survival showed that no significant differences. Six of the 28 lymph nodes (21.4%) exhibited consistent NF-kappaB activity. Three of the eleven cases that transformed to aggressive lymphoma were positive for activated NF-kappaB. Further research to clarify the significance of constitutive NF-kappaB activity in follicular lymphoma is therefore warranted.

CD20-positive T-cell malignancy is a rare disease. We report a case of CD20-positive T-cell large granular lymphocyte leukemia (T-LGLL). The leukemic cells were positive for CD20 and T cell markers, such as CD3, CD4, CD5, CD8 and CD57. A monoclonal rearrangement of the T-cell receptor (TCR) beta chain gene was detected. Twenty-three cases of well-documented CD20-positive T-cell malignancies were reviewed. Most cases were mature T-cell malignancies, especially exhibiting a cytotoxic T-cell phenotype, despite a diversity of the pathological diagnoses. Additional cases must be evaluated to clarify the implications of CD20 expression on T-cell malignancies and to elucidate whether such cases constitute a distinct biologic and clinical disease entity. The accumulation of cases will help to facilitate provision of a proper treatment for CD20-positive T-cell malignancies in the future.

Background: Changes of serum IgG oligosaccharide chain structure have been found in B cell lineage tumors and autoimmune diseases. Currently, the cancer-associated carbohydrate epitopes CA72-4 and CA15-3 are used as serum tumor markers. In the present study, we analyzed the structure of serum IgG oligosaccharide chains in prostate cancer (PCa) patients using the simple new method of fluorophore-associated carbohydrate electrophoresis (FACE). We also evaluated the relationship between changes of serum IgG oligosaccharide chain structure and serum concentration of prostate-specific antigen (PSA)., Materials and Methods: The structure of serum IgG oligosaccharide chains from 12 PCa patients (6 localized cancer, 6 metastatic cancer) and 10 healthy controls was evaluated by FACE. PSA levels in serum were determined by enzyme immunoassay., Results: Fr 1 (monogalactosyl oligosaccharide) and Fr 2 (digalactosyl oligosaccharide) decreased significantly (p<0.05), while Fr 4 (agalactosyl IgG oligosaccharide) increased with PCa tumorprogression. The Fr 4/Fr 1+2 ratio in metastatic PCa patients was significantly higher than in healthy controls (p<0.05), and there was a significant correlation (r=0.84, p<0.05) between serum PSA levels and the Fr 4/Fr 1+2 ratio in all patients with PCa., Conclusion: The changes of serum IgG oligosaccharide chain structure with PCa progression are based on the abnormality of glycosylation in PCa metastasis. Therefore, the analysis of serum IgG oligosaccharide chain structure by FACE may be an auxiliary indicator of PSA for monitoring PCa progression.