Examination of the inhibitory effects of interferon-gamma on interleukin-4-induced stimulation of resting B cells from NZB/NZW F1 mice.

Percoll fractionation of NZB/NZW F1 mouse B cells revealed an increased ratio of low-density fraction ('activated' B cell fraction) and a decreased ratio of high-density fraction ('resting' B cell fraction), in comparison to normal mouse B cells. Resting B cells of B/W F1 mice were hyperresponsive to interleukin-4 (IL-4), with increased proliferation and IgG anti-DNA antibody production, in comparison to normal mice. The hyper-responses of resting B cells from NZB/NZW F1 mice to IL-4 were affected with dose dependency by interferon-gamma (INF-gamma); specifically, cell proliferation and anti-nuclear antibody production were suppressed in the presence of IFN-gamma. This suppressor action of IFN-gamma was most noticeable when it was added to the culture system simultaneously with IL-4. These findings suggested that the abnormally activated state of NZB/NZW F1 mice B cells can be attenuated by the action of IFN-gamma on resting B cells.     

The Diagnosis and Treatment of Primary Pulmonary Artery Sarcoma: Two Case Reports

Pulmonary artery sarcoma (PAS) is considered a very rare tumor with a poor prognosis. We herein report two cases of PAS that were diagnosed by positron emission tomography (PET)/computed tomography (CT). In both cases, PET was an effective option for diagnosing tumors, and surgical resection was a valid treatment for these diseases. If a pulmonary artery tumor is suspected, PET/CT is useful for diagnosing PAS and very helpful for choosing the surgical treatment strategy.     

The role of circulating immune complexes in the pathogenesis of Graves' disease

It has recently been reported that many immunological abnormalities including the presence of TSH-receptor antibody (TRAb) were found in Graves' disease (GD). Circulating immune complexes (CIC) have also been detected in the serum of patients with GD as observed in systemic lupus erythematosus, which is thought to be a typical model of immune complex disease. The role of CIC in pathogenesis of hyperthyroidism, however, remains to be elucidated. Therefore, to clarify pathophysiological functions of CIC in GD, the levels of it in those patients were compared with their symptoms, those of TRAb, and lymphoblastogenesis (LBG) induced by phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). The subjects were forty patients with GD without any medication, one hundred and nine patients with GD on medication with methimazole (MMI), and fifteen healthy volunteers. CIC was measured by three different methods; polyethyleneglycol precipitation method (PEG), Clq binding assay (Clq), and Protein A binding assay (PA). The normal range was estimated with the mean plus or minus two times the standard deviation of normal controls. In untreated GD, CIC determined by PEG, Clq and PA widely distributed from normal range to high levels. The positive rates of CIC determined by PEG, Clq, PA, and any one method of these three were 17.5%, 22.5%, 30.0% and 52.5%, respectively. LBG using incorporation of tritiated thymidine showed the decreases in PHA and Con A, and the increases in PWM in patients with GD. The positive rates of CIC determined by PEG and PA were significantly higher in patients without goiter or with small one than those with large one (p less than 0.05). CIC measured by all three of PEG, Clq and PA showed negative correlation with TRAb significantly (p less than 0.05, p less than 0.01, p less than 0.01, respectively). On the other hand, CIC measured by Clq showed significant negative correlation with serum thyroxine concentration (p less than 0.01). The levels of CIC, TRAb and PWM-induced LBG decreased following the tapering dose of MMI sufficient to keep patients in euthyroid state. In consequence, there were no longer any correlations between CIC and TRAb after thyroid function was normalized. These observations suggest that CIC's which have huge molecular weight or have ability to bind Fc receptor on K cell, macrophage, neutrophil, and other immune cells may be one of the factors to inhibit the goitrogenic action of TRAb, and that CIC's which have ability to activate the complement system may be one of the factors to inhibit the stimulation of secretion of thyroid hormone by TRAb.(ABSTRACT TRUNCATED AT 400 WORDS)     

Microscopic polyangitis as a possible cause of diabetes insipidus

Received: 29 March 2002 / Accepted: 28 June 2002 Correspondence and offprint requests to: M. Funauchi, Division of Hematology, Nephrology and Rheumatology, Department of Internal Medicine, Kinki University School of Medicine 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Osaka, Japan. Tel: ++81-723-66-0221, ext. 3128; Fax: ++81-723-68-3732 (direct); E-mail: funauchi@med. kindai.ac.jp     

Increased interleukin-4 production by NK T cells in systemic lupus erythematosus.

It has been reported that production of interleukin (IL)-4, a T helper (Th)-2-type cytokine, might play an important role in the pathogenesis of systemic lupus erythematosus (SLE). On the other hand, it is known that NK1.1(+) cells which belong to CD4, CD8 double-negative, or CD4(+) cells are associated with initial IL-4 production and Th2 differentiation in mice although human equivalent cells are unknown. In order to study the profile of IL-4-producing cells in SLE, cytoplasmic IL-4 and various surface antigens on peripheral mononuclear cells were analyzed. Peripheral mononuclear cells were stimulated for 5 h by phorbol ester and ionomycin in the presence of monensin, fixed, and permeabilized with paraformaldehyde and saponin solution. Then cytoplasmic IL-4 and various surface antigens were analyzed by flow cytometry. IL-4-producing cells in SLE were phenotypically the same as those which produce IL-4 normally and frequently bore activated T-cell (CD7, CD25, CD28, CD29) and NK-cell markers (CD56, CD57). Double-negative T cells and CD57(+) T cells were increased in number and were more frequently positive for cytoplasmic IL-4 in SLE compared with normal controls and various infectious diseases. It was suggested that T cells with NK cell markers, CD57(+) T cells, which are known to extrathymically differentiate, might be involved in the pathogenesis of SLE as a counterpart of mouse NK1.1(+) cells.