Plasmacytoma of Lymph Node Recurrent Lymphadenopathy Terminating in Plasma Cell Dyscrasia with Polyneuropathy and Endocrine Disturbances

A case with lymphadenopathy of the left side of the neck in a 38-year-old male is described. He had a history of several relapses of about 10 years duration. Swollen lymph nodes were histologically similar to those of the hyaline-vascular type of Castleman's disease, but contained clear-cut lymph sinus and a sheet-like proliferation of plasma cells. Lymph follicles showed proliferation and atrophic germinal centers, in which cellular hypertrophy in the wall of ramifying small blood vessels, called angiosclerosis, was frequently encountered. During its progress, the patient developed plasmacytoma of the lymph nodes with varied clinical manifestations such as polyneuropathy, disturbance of gait, unusual perspiration, hirsuitism, gynecomastia, bilateral papilledema, and albumino-cytologic dissociation in cerebrospinal fluid.     

Vinyl polymerization by metal complexes, 14. Synthesis of 2-substituted and 2,4-disubstituted imidazole-copper(II) complexes as initiator systems for vinyl polymerization

A series of the copper(II) complexes of the type CuL₄X₂ (L: ligand, X: anion) was prepared with the following substituted imidazoles as ligands 2-ethyl- ( 1a ), 2-ethyl-4-methyl- ( 1b ), 2-phenyl- ( 1c ), 2-undecyl- ( 1d ), and 2-heptadecylimidazole ( 1e ). The structures of these complexes were confirmed by elemental analysis, reflection spectra of the crystals as well as IR-spectroscopy. Polymerization of acrylonitrile was tested in the presence of each imidazole-copper(II) complex in dimethyl sulfoxide solution.     

A case of malignant duct-islet cell tumor of the pancreas immunohistochemical and cytofluorometric study.

A rare duct-islet cell tumor of the pancreas was studied using immunohistochemical, cytofluorometric and histochemical methods. Histology and immunohistochemistry revealed that the tumor contained two distinct cell types; islet cell-like neuroendocrine cells and exocrine duct cell components, suggesting an endodermal origin for both types. The cells showed marked pleomorphism an vascular and perineural invasion at the tumor periphery. Cytofluorometric study of the tumor cell DNA revealed an increased mean nuclear DNA content, without any aneuploidy. Histochemically, the tumor cells contained an increased number of argyrophilic nucleolar organizer regions (AgNORs) in their nuclei. The malignant potential of this duct-islet cell tumor was suggested.     

Kappa-type light chain crystal storage histiocytosis.

An autopsy case of systemic histiocytosis with excessive deposition of kappa-type light chain crystals was reported in a 58 year-old man who had consistently showed kappa-type light chain paraproteinemia, Bence Jones proteinuria and hypogammaglobulinemia for about 10 years until his death. However, no bony destruction was found by repeated X-ray examinations. At autopsy, extensive hyperplasia of crystal-storing histiocytes was observed in the bone marrow, spleen, liver, lymph nodes, interstitial tissues of visceral organs and loose connective tissues. In the bone marrow and some other tissues, mild proliferation of plasmocytoid cells containing small crystals were found. Histochemically the crystals positively stained with various methods for amino acids and proteins, especially with Weigerts' method for fibrin. Ultrastructurally intralysosomal crystal deposition was confirmed in the storage histiocytes and derivation of the crystals from Golgi's sacculi in the plasmocytoid cells was suggested. Biochemically the crystals were regarded as mainly consisting of dimers of a variable half of light chain immunoglobulin and immunochemically and immunohistochemically reacted to anti-kappa type light chain serum. Such a generalized storage histiocytosis may be secondarily induced by immunoglobulin synthesized in plasmocytoid cells.     

Chymase inhibitor ameliorates eosinophilia in mice infected with Nippostrongylus brasiliensis

BACKGROUND: Chymase is a chymotrypsin-like serine protease primarily stored in mast cells. Infection with helminth parasites is known to increase the level of mast cell chymase in the jejunum and serum in mice. The aim of the present study is to elucidate the role of chymase in helminth infection. METHODS: Chymase inhibitor SUN-C8257 was administered to mice infected with the nematode Nippostrongylus brasiliensis, and the number of eosinophils in the blood, serum IgE levels and fecal egg counts were determined. RESULTS: Administration of SUN-C8257 significantly inhibited blood eosinophilia in BALB/c mice infected with N. brasiliensis. The effect of SUN-C8257 was specific for eosinophils, in that it affected neither the number of total leukocytes nor serum IgE levels. SUN-C8257 did not alter the fecal egg counts in this model, showing that SUN-C8257 has no effect on infectivity and expulsion of the nematode. N. brasiliensis infection induced eosinophilia in mast cell-deficient mice (W/W(v)) as well as their littermates (+/+), and SUN-C8257 inhibited the eosinophilia in +/+ mice but not in W/W(v) mice. These results suggest that the eosinophil number may be regulated by different mechanisms in W/W(v) and +/+ mice, and that the effect of SUN-C8257 on nematode-induced eosinophilia is probably due to chymase inhibition. CONCLUSIONS: Chymase released by activated mast cells may play a role in helminth-induced eosinophilia.     

Bacterial superantigen-treated intestinal epithelial cells upregulate heat shock proteins 25 and 72 and are resistant to oxidant cytotoxicity

While the pathological events evoked by infection are commonly described, effective host responses to bacteria and their products should primarily be protective. Heat shock protein (Hsp) expression is upregulated by many stimuli and serves to maintain intracellular protein integrity. The ability of the prototypic superantigen, Staphylococcus aureus enterotoxin B (SEB) to induce Hsps was investigated with BALB/c mice and by in vitro addition to the murine small intestinal epithelial cell line MSIE. SEB-treated (5 or 100 microg intraperitoneally) mice revealed increased Hsp25 and Hsp72, but not Hsc73, in jejunal lymphocytes and epithelial cells. A similar Hsp response to SEB occurred in MSIE cells and was preceded by activation of the ERK1/2 and p38 mitogen-activated protein kinases but not the SAPK/JNK pathway; pharmacological inhibition of ERK1/2, but not p38, significantly reduced SEB-induced Hsps. Moreover, SEB-treated MSIE cells were protected against oxidant-induced cytotoxicity (measured by 51Cr release) and F-actin depolymerization. Thus, SEB exposure results in a rapid induction of the Hsp25 and Hsp72 in intestinal epithelial cells, both directly and through lymphocyte activation, and we suggest that this event is important in protecting the gut from damage by Staphylococcus infection or in the reparatory process and may be a generalized response to lumen-derived bacterial toxins.     

CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer.

Intestinal metaplasia is a key event in multistep gastric carcinogenesis. CDX2, a master regulator of intestinal phenotype, was shown to play a tumor-suppressive role in colon cancer. However, it was reported to be expressed in nearly all gastric intestinal metaplasia and many gastric cancers. As CDX2 is differentially expressed in normal stomach and intestine, we sought to relate the CDX2 expression to gastrointestinal differentiation along gastric carcinogenesis. The expression of CDX2 protein in gastric intestinal metaplasia, dysplasia and cancer was examined and related to their gastrointestinal differentiation. CDX2 expression was significantly decreased in incomplete intestinal metaplasia, which expresses both gastric mucins (MUC5AC and MUC6) and intestinal mucin (MUC2), compared with complete intestinal metaplasia, which expresses intestinal mucin (MUC2) only. Although incomplete intestinal metaplasia morphologically resembles colon, its CDX2 expression was apparently lower than that in the normal colon. Moreover, CDX2 expression was progressively reduced in gastric dysplasia and cancer. The CDX2 expression in gastric cancer was also inversely correlated with the expression of gastric mucins. As incomplete intestinal metaplasia is associated with higher risk of gastric cancer, its lower CDX2 expression compared with that in complete intestinal metaplasia and normal colon epithelium resolved the current contradiction between the tumor-suppressive role of CDX2 in the colon and the high prevalence of CDX2 in intestinal metaplasia. Further decrease of CDX2 expression in gastric dysplasia and cancer suggests that CDX2 plays a similar anticarcinogenic role in intestinal metaplasia as it does in colon. Intestinal metaplasia or dysplasia with low expression of CDX2 may serve as predictive markers for gastric cancer.     

Expression of BAFF-R (BR3) in normal and neoplastic lymphoid tissues characterized with a newly developed monoclonal antibody

BAFF-receptor (BAFF-R) is required for the successful maturation and survival of B-cells. We developed an anti-human BAFF-R monoclonal antibody (mAb), 8A7. The reactivity of 8A7 in normal and neoplastic tissue was examined by performing immunohistochemistry on paraffin-embedded sections. 8A7 reacted with lymphocytes in the mantle and marginal zones, but not with lymphocytes in the interfollicular area. Lymphocytes in the germinal centers were found to be negative or occasionally weakly positive for 8A7. BAFF-R expression was found only in B-cell lymphoma (44/80, positive cases/examined cases): B-lymphoblastic lymphoma 0/3, B-chronic lymphocytic leukemia/small lymphocytic lymphoma 4/4, mantle cell lymphoma 9/11, follicular lymphoma 10/14, diffuse large B-cell lymphoma (DLBCL) 11/25, marginal zone B-cell lymphoma 8/10, lymphoplasmacytic lymphoma 2/2, plasma cell myeloma 0/2, and Burkitt lymphoma 0/9, but not in T/NK cell lymphomas (0/19) or Hodgkin lymphoma (0/10). BAFF-R was expressed in most low-grade B-cell neoplasms and a small number of DLBCL, suggesting that BAFF-R may play an important role in the proliferation of neoplastic lymphoid cells. Thus, the mAb is very useful for further understanding of both healthy B-cell biology and its pathogenic neoplasms.     

Simple method for the identification of oxidative fibers in skeletal muscle

Skeletal muscle is composed of several different types of myofiber: slow oxidative (SO), fast glycolytic oxidative and fast glycolytic. However, the classification is usually determined by myosin heavy chain typing rather than by metabolic index. In this study, the oxidative metabolic index was investigated as a possible method of myofiber typing. Myoglobin, which is involved in oxygen transport and storage in myofibers, and mitochondria, which are the central organelles for oxidative metabolism, were studied. High levels of myoglobin and mitochondria are believed to exist in SO fibers, but the current study showed that they are considerably richer in some fast type fibers. As myofiber typing using the oxidative metabolic index is important physiologically, an attempt was made to find a simple method for this purpose. Some mitochondrial proteins have been observed to auto-fluoresce but until now this effect was too faint to detect easily. Owing to the recent advances in cooling charge-coupled device technology, such auto-fluorescence can now be used for myofiber typing, and the simple and rapid method for doing so is reported here.     

Inhibition of MAP kinase activity moderates changes in expression and function of Cx32 but not claudin-1 during DNA synthesis in primary cultures of rat hepatocytes

The signal transduction pathways and activation of the MAP kinase or PI3 kinase signaling cascade regulate a variety of cellular processes, including proliferation and differentiation in hepatocytes. To elucidate the mechanisms of signal transmission required for the regulation of gap and tight junctions during DNA synthesis in rat hepatocytes, we determined changes of expression and function of gap and tight junctions of cells grown in primary culture, using inhibitors of signaling pathways for MAP kinase (PD98059) and PI3 kinase (LY294002). During the stimulation of DNA synthesis induced by epidermal growth factor (EGF), immunoreactivity and mRNAs of gap junction protein Cx32 and of tight junction protein claudin-1 markedly decreased with reduction of gap junctional intercellular communication (GJIC) and the fence function of tight junctions. In Western blots, whole-cell lysate of claudin-1 protein decreased and phosphorylated Cx32 protein in the insoluble fraction of Triton X-100 increased during the stimulation of DNA synthesis. During reinhibition of DNA synthesis, the changes of Cx32 and claudin-1 returned to control levels, as did both functions. In treatment with the inhibitors before DNA synthesis, PD98059 inhibited the changes of expression and function of Cx32, but not claudin-1, without inhibition of cell growth, whereas LY294002 completely inhibited cell growth. These findings indicate that the PI3 kinase pathway rather than the MAP kinase pathway plays an important role for EGF-induced proliferation of rat hepatocytes, and that changes of Cx32 in hepatocytes during the stimulation of DNA synthesis may be in part controlled through MAP kinase. Furthermore, Cx32, but not claudin-1, protein may be a target of activated MAP kinase in hepatocytes.