High serum matrix metalloproteinase 3 is characteristic of patients with paraneoplastic remitting seronegative symmetrical synovitis with pitting edema syndrome

Recently, it was reported that remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome could be complicated with solid tumors. In a retrospective, multicenter study between October, 2003 and September, 2010, we investigated the characteristics of patients with paraneoplastic RS3PE syndrome who fulfilled following criteria: (1) bilateral pitting edema of hands or feet or both, (2) sudden onset of polyarthritis, and (3) age >50?years, (4) seronegativity for rheumatoid factor (RF). A total of 33 cases fulfilled the above criteria. Eight patients (seven men and one woman) developed cancer within 2?years of RS3PE syndrome onset. There was no significant difference between the neoplastic and nonneoplastic groups in the proportions of patients with fever, symmetrical polyarthritis, pitting edema, and good response to corticosteroids. Serum matrix metalloproteinase 3 (MMP-3) level (median 437.3?ng/ml) in the paraneoplastic RS3PE patients was significantly higher than that in patients without neoplasia (median 114.7?ng/ml) (p?相似文献   

A case of Fabry's disease detected by renal biopsy findings

A 39 year-old man was found to have mild proteinuria by urinary examination since one year ago. He was for the first time diagnosed as having Fabry's disease by histopathological and electronmicroscopic findings of the renal biopsy specimens, which showed the presence of numerous vacuolated cells and electron dense bodies inside the cells. The level of WBC alpha-galactosidase was significantly lower than normal level. The pedigree of this patient showed a familial history of various types of renal disease. One of the patient's brothers also showed decreased level of WBC alpha-galactosidase, who has been treated by maintenance hemodialysis for 2 years. It is concluded that early diagnosis of this disease through renal biopsy and WBC alpha-galactosidase level is important to manage the future course of patients with Fabry's disease.     

Expression of the intestinal T-lymphocyte-associated-molecule recognized by the HML-1 antibody on mononuclear cells from HTLV-I-infected subjects

We investigated the expression of a monoclonal antibody (HML-1) defined antigen that appears on human intestinal T-lymphocytes in HTLV-I-related disease. We studied 25 ATL, and 24 healthy HTLV-I carriers. Patients with acute ATL showed a variety of the expression of the HML-1 antigen (range 0.4–74.8%). HML-1 expression on mononuclear cells (MNCs) in blood from patients with chronic ATL ranged from 1.7–43.6% (mean 13.5%). This level of expression was less than that of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of expression ranged from 1.6–13.3% (mean 8.0%). In contrast to patients wtih acute ATL, MNCs from patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and B-cell type chronic lymphocytic leukemia (B-CLL) did not express the HML-1 antigen, except for the 2 patients with ALL. Healthy HTLV-I carriers and healthy controls also were negative for HML-1 reactivity. In acute ATL, patients with gastrointestinal tract infiltration tended to have high expression of the HML-1 epitope. After stimulation with phytohemagglutinin (PHA), healthy HTLV-I carriers showed significantly increased expression of the HML-1 epitope (P < 0.05). Recently, the β7 integrin family has been found to play a specific role in mucosal localization or adhesion, and HML-1 protein was found to match the deduced β7 N-terminal sequence. We propose that the cellular gene responsible for HML-1 epitope expression may, like IL-2, IL-2R, etc., be transactivated by infection with HTLV-I, and that HML-1 antigen gene expression by HTLV-I infection may lead to infiltration of ATL cells with highly expressed HML-1 epitope into the gut mucosa.     

Pharmacokinetics and cell trafficking dynamics of 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride (FTY720) in cynomolgus monkeys after single oral and intravenous doses

The pharmacokinetics and cell trafficking dynamics of 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride (FTY720), a novel immunosuppressive agent, were examined in cynomolgus monkeys (three males and three females). After single doses of 0.1 mg/kg p.o. or i.v. bolus and 1 mg/kg p.o. were administered to the animals, the concentrations of FTY720, and the numbers of lymphocytes, CD20+CD2-B cells, and CD2+CD20-T cells in blood were measured over 23 days. A linear three-compartment model characterized the time course of FTY720 concentrations with a terminal half-life of about 31 h, clearance of about 0.53 l/h/kg, and bioavailability of about 38%. The dynamic responses were not area under the curve (or dose) proportional for either males or females. An indirect response model with a distribution pool captured the cell trafficking data for all doses for each cell type, where initial blood counts (R(0)) were about 7650, 2100, and 5250 cells/microl; maximum fractional inhibition (I(max)) about 0.88, 0.85, and 0.91; influx (k(in)) about 6014, 1312, and 5662 cells/microl/h; efflux (k(out)) about 0.798, 0.555, and 1.08 h(-1); intercompartmental k(cp) about 0.134, 0.192, and 0.082 h(-1); and intercompartmental k(pc) rate constants about 3.9 x 10(-4), and 0.016 and 8.9 x 10(-6) h(-1) for lymphocytes, B cells, and T cells, respectively. The inhibition concentration IC(50) was about 0.48 microg/l for all cells, which was remarkably low. The apparent distribution volumes of peripheral pool (V(p)) were markedly larger than blood volume (V(b)) for all cells. The I(max) for cell trafficking was achieved at doses smaller than that producing graft protection, indicating stronger central than peripheral effects of this drug. The profound cell trafficking effects of FTY720 can be readily captured and interpreted with an extended indirect response model.     

SF-1/Ad4BP transforms primary long-term cultured bone marrow cells into ACTH-responsive steroidogenic cells

Bone marrow stem cells develop into haematopoietic and mesenchymal lineages, but have not been known to participate in steroidogenic cell production. Steroidogenic factor 1 (SF-1), also designated adrenal 4 binding protein (Ad4BP), is an essential orphan nuclear receptor for steroidogenesis as well as for adrenal and gonadal gland development. In the present study, we revealed that the adenovirus-mediated forced expression of SF-1 can transform cultured primary long-term cultured bone marrow cells into steroidogenic cells, showing the de novo synthesis of multiple steroid hormones in response to adrenocorticotropic hormone (ACTH). This finding may provide an initial step in innovative autograft cell transfer therapy for steroid hormone deficiencies.     

Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells

It is widely known that IL-4 and IL-13 act on various kinds of cells, including B cells, resulting in enhancement of proliferation, class switching to IgE and expression of several surface proteins. These functions are important for the recognition of the various antigens in B cells and are known to be involved in the pathogenesis of allergic diseases. However, it has not been known whether IL-4/IL-13 is involved in the metabolism of various kinds of xenobiotics including 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), and it remains undetermined whether TCDD, an environmental pollutant, influences IgE production in B cells, exaggerating allergic reactions. We identified IL-4- or IL-13-inducible genes in a human Burkitt lymphoma cell line, DND-39, using microarray technology, in which the AHR gene was included. The AHR gene product, the aryl hydrocarbon receptor (AhR), was induced by IL-4 in both mouse and human B cells in a STAT6-dependent manner. IL-4 alone had the ability to translocate the induced AhR to the nuclei. TCDD, a ligand for AhR, rapidly degraded the induced AhR by the proteasomal pathway, although IL-4-activated AhR sustained its expression. AhR activated by IL-4 caused expression of a xenobiotic-metabolizing gene, CYP1A1, and TCDD synergistically acted on the induction of this gene by IL-4. However, the induction of AhR had no effect on IgE synthesis or CD23 expression. These results indicate that the metabolism of xenobiotics would be a novel biological function of IL-4 and IL-13 in B cells, whereas TCDD is not involved in IgE synthesis in B cells.     

c-fos overexpression in splenic B cells augments development of marginal zone B cells

Marginal zone (MZ)-B cells participate in very early immune responses and play a pivotal role in the first-line of defense against blood-borne Ags including bacterial LPS. Since splenic B cells from c-fos transgenic (H2-c-fos) mice are hyper-sensitive to LPS stimulation, we examined LPS-sensitivity of MZ-B cells in the spleen of H2-c-fos mice. Here, we show that proliferation of MZ-B cells from H2-c-fos mice stimulated with LPS was larger than that from control mice. Proliferation and IgM production of the H2-c-fos MZ-B cells were also larger than those of splenic follicular (FO)-B cells from the H2-c-fos mice, suggesting that c-fos overexpression augments LPS-sensitivity of MZ-B cells more than that of FO-B cells. Furthermore, the number of MZ-B cells but not that of FO-B cells in the spleen of H2-c-fos mice was two- to three-fold larger than that in control littermates. The number of transitional type II (T2)-B cells in H2-c-fos mice was also larger than that of control littermates. However, the number of transitional type I (T1)-B cells in the spleen of H2-c-fos mice was not larger than that of control mice. Moreover, this c-fos effect on differentiation of MZ-B cells was intrinsic in B cells by the competitive repopulation assay with hematopoietic stem cells of H2-c-fos and control mice. These results suggest that c-fos overexpression in B cells augments differentiation and accumulation of MZ-B cells.