No abstract

To clarify the pathogenesis of insulitis in the nonobese diabetic (NOD) mouse, an animal model for human insulin-dependent diabetes mellitus, T-lymphocyte-depleted NOD mice (B mice) were adoptively transferred with spleen and lymph node cells from cyclophosphamide-treated NOD mice after separating the cells with monoclonal antibodies against various T-lymphocyte surface antigens plus complement. Light-microscopic and immunohistochemical studies were also performed to investigate the lymphocytic infiltrations. The incidence of insulitis detected in B mice was much lower when compared with that of the lesion naturally occurring in the NOD mouse. However, higher incidence of insulitis was inducible in B mice by transferring unfractionated lymphoid cells from NOD mice. When the Thy1+ cell-depleted fraction was transferred into the B mice, no increase in the incidence of insulitis was observed. The Lyt1+ or L3T4+ cell-eliminated fraction was also unable to transfer insulitis. Conversely, donor cells depleted of Lyt2+ components successfully induced insulitis in the recipient B mice. These data were consistent with the immunohistochemical study, which showed that the main phenotype of the cells infiltrating the islets was L3T4+. These results suggest the importance of L3T4+Lyt2- T-lymphocytes in the pathogenesis of insulitis in NOD mice.

Ferritin is an iron-storage protein and its serum level is known to increase in the patient of with inflammation and malignant tumor. To further elucidate the difference between ferritins from normal human liver tissue and that of cancer cells, their sialic acids were analyzed. The Western blot analysis and the cytochemical staining using anti-NeuGc antiserum indicated that ferritins from the human hepatocarcinoma tissue and malignant K562 cells contain NeuGc, but that from the normal liver does not. The result was also confirmed by HPLC analysis and MALDI-TOF/MS analysis of sialic acids which were derivatized by the DMB method. It was also shown that the sialic acid content in hepatocarcinoma ferritin was much higher than that in the normal liver ferritin. These results suggest that normal and cancerous liver ferritins are qualitatively and quantitatively different in sialylation. In addition, K562 cells were shown to express NeuGc even if the cells were cultured in serum-free media which lack NeuGc. This is of interest from the current concept that expression of NeuGc in human cells is due to uptake and utilization of exogenous NeuGc.

The specific antiserum against a type of ferritin that is especially common to leukemia cells and the placenta was used to test, by countercurrent immunoelectrophoresis, sera from humans with various diseases. The best results were obtained with leukemia; patients with chronic myelogenous leukemia in blastic phase, acute myelogenous leukemia, lymphogenous leukemia, and unclassifiable juvenile leukemia frequently showed a positive reaction, but patients with chronic myelogenous leukemia in static phase did not. The average incidence of positive reaction among all leukemia patients was 54.0%. Patients with other malignant tumors (i.e., multiple myeloma, malignant lymphoma and carcinomas of the stomach, rectum, and liver) also often showed a positive reaction. The average incidence of positive reaction among all the patients with malignant diseases of the hematopoietic system, except for leukemia, was 34.3%, and that among patients with nonhematologic malignant neoplasms was 36.8%. However, the incidence of a positive reaction in patients with benign diseases and healthy individuals was less than 3%.

Summary.We describe a case of Waldenström's macroglobulinaemia with two M-components (IgM and IgG) with the same l light chain. Southern blot analysis of bone marrow cells showed rearrangements of immunoglobulin heavy and l light chain genes.Sequencing of the complementarity determining region 3 of the two g and m transcripts showed 100% homology. Immunofluorescence study showed that most cells stained for both IgG and IgM. These findings indicated that a single population of cells was expressing two isotypic variants of IgG and IgM, as the genes responsible for production of both components had the same origin.