岡崎 仁昭

Introduction: Previous studies indicate that professional identity formation (PIF), the formation of a self-identity with the internalised values and norms of professionalism, may influence self-regulated learning (SRL). However, it remains unclear whether a PIF-oriented intervention can improve SRL in clinical education. The aim of this study was to explore whether a PIF-oriented mentoring platform improves SRL in a clinical clerkship. Methods: A mixed-methods study was conducted. Forty-one students in a community-based clinical clerkship (CBCC) used a PIF-oriented mentoring platform. They articulated the values and norms of professionalism in a professional identity essay, elaborated on future professional self-image, and reflected on their current compared to future selves. They made a study plan while referring to PIF-based self-reflection and completed it. The control group of 41 students completed CBCC without the PIF-oriented mentoring platform. Changes in SRL between the two groups were quantitatively compared using the Motivated Strategies for Learning Questionnaire. We explore how PIF elements in the platform affected SRL by qualitative analysis of questionnaire and interview data. Results: A moderate improvement in intrinsic goal orientation (p = 0.005, ε2 = 0.096) and a mild improvement in critical thinking (p = 0.041, ε2 = 0.051) were observed in the PIF-oriented platform group. Qualitative analysis revealed that the PIF-oriented platform fostered professional responsibility as a key to expanding learning goals. Gaining authentic knowledge professionally fostered critical thinking, and students began to elaborate knowledge in line with professional task processes. Conclusion: A PIF-oriented mentoring platform helped students improve SRL during a clinical clerkship.

<title>Abstract</title><sec> <title>Background</title> Developing self-regulated learning in preclinical settings is important for future lifelong learning. Previous studies indicate professional identity formation, i.e., formation of self-identity with internalized values and norms of professionalism, might promote self-regulated learning. We designed a professional identity formation-oriented reflection and learning plan format, then tested effectiveness on raising self-regulated learning in a preclinical year curriculum. </sec><sec> <title>Methods</title> A randomized controlled crossover trial was conducted using 112 students at Jichi Medical University. In six one-day problem-based learning sessions in a 7-month pre-clinical year curriculum, Groups A (<italic>n</italic> = 56, female 18, mean age 21.5y ± 0.7) and B (<italic>n</italic> = 56, female 11, mean age 21.7y ± 1.0) experienced professional identity formation-oriented format: Group A had three sessions with the intervention format in the first half, B in the second half. Between-group identity stages and self-regulated learning levels were compared using professional identity essays and the Motivated Strategies for Learning Questionnaire. </sec><sec> <title>Results</title> Two-level regression analyses showed no improvement in questionnaire categories but moderate improvement of professional identity stages over time (<italic>R</italic>² = 0.069), regardless of timing of intervention. </sec><sec> <title>Conclusions</title> Professional identity moderately forms during the pre-clinical year curriculum. However, neither identity nor self-regulated learning is raised significantly by limited intervention. </sec>

The objective was to investigate the clinical and histological features of liver dysfunction in patients with polymyositis (PM) or dermatomyositis (DM).A total of 115 patients (38 with PM and 77 with DM), who were admitted to our hospital between 2001 and 2012, were retrospectively reviewed. Liver dysfunction was defined as an alanine transaminase (ALT) level ≥ 60 U/l and a disproportionate ALT elevation relative to the creatine kinase level. The histological findings from liver biopsies were also assessed.The frequencies of liver dysfunction were 3% and 17% in the patients with PM and DM, respectively. Liver dysfunction was not observed in the patients who had malignancies. Among the patients with DM with no malignancies (n = 50), 20% had liver dysfunction, and all of the patients with liver dysfunction were positive for the anti-melanoma differentiation-associated gene 5 (MDA5) antibody. Compared with those in the patients who did not have liver dysfunction, the ALT, alkaline phosphatase, γ-glutamyl transferase, and KL-6 levels were significantly elevated in the patients who had liver dysfunction. Six patients, comprising four with DM and two with PM, underwent liver biopsies, and the common histological findings associated with DM were steatosis, hepatocyte ballooning, increases in the pigmented macrophage numbers, and glycogenated nuclei. Hemophagocytosis was detected in two of three patients with DM who underwent liver biopsies and bone marrow aspirations. In conclusion, Liver dysfunction might be an extramuscular manifestation in patients with DM who are anti-MDA5 antibody-positive. Steatosis and hepatocyte ballooning could be common histological features.

Background and objectives: Previous studies support the notion that East Asian medical students do not possess sufficient self-regulation for postgraduate clinical training. However, some East Asian physicians who are employed in geographically isolated and educationally underserved rural settings can self-regulate their study during the early phase of their postgraduate career. To explore the contextual attributes that contribute to self-regulated learning (SRL), we examined the differences in self-regulation between learning as an undergraduate and in a rural context in East Asia. Methods: We conducted interviews and diary data collection among rural physicians (n = 10) and undergraduates (n = 11) in Japan who undertook self-study of unfamiliar diseases. We analyzed three domains of Zimmerman’s definition of SRL: learning behaviors, motivation, and metacognition using constructivist grounded theory. Results: Rural physicians recognized their identity as unique, and as professionals with a central role of handling diseases in the local community by conducting self-study. They simultaneously found themselves being at risk of providing inappropriate aid if their self-study was insufficient. They developed strategic learning strategies to cope with this high-stakes task. Undergraduates had a fear of being left behind and preferred to remain as one of the crowd with students in the same school year. Accordingly, they copied the methods of other students for self-study and used monotonous and homogeneous strategies. Conclusions: Different learning contexts do not keep East Asian learners from being self-regulated. Awareness of their unique identity leads them to view learning tasks as high-stakes, and to initiate learning strategies in a self-regulated manner. Teacher-centered education systems cause students to identify themselves as one of the crowd, and tasks as low-stakes, and to accordingly employ non-self-regulated strategies.

Background: Progress testing (PT) is used in Western countries to evaluate students' level of functional knowledge, and to enhance meaning-oriented and self-directed learning. However, the use of PT has not been investigated in East Asia, where reproduction-oriented and teacher-centered learning styles prevail. Here, we explored the applicability of PT by focusing on student perceptions. Methods: Twenty-four students from Years 2, 3, and 5 at Jichi Medical University in Japan attended a pilot PT session preceded by a brief introduction of its concept and procedures. Variations in obtained test scores were analyzed by year, and student perceptions of PT were explored using focus groups. Results: Formula scores (mean ± standard deviation) in Years 2, 3, and 5 were 12.63 ± 3.53, 35.88 ± 14.53, and 71.00 ± 18.31, respectively. Qualitative descriptive analysis of focus group data showed that students disfavored testing of medical knowledge without tangible goals, but instead favored repetitive assessment of knowledge that had been learned and was tested on a unit basis in the past in order to achieve deep learning. Further, students of all school years considered that post-test explanatory lectures by teachers were necessary. Conclusions: East Asian students' perceptions indicated that, in addition to their intensive memorization within narrow test domains compartmentalized by end-of-unit tests, the concept of PT was suitable for repetitive memorization, as it helped them to integrate their knowledge and to increase their understanding. Post-test explanatory lectures might lessen their dislike of the intangible goals of PT, but at the expense of delaying the development of self-directed learning. Key issues for the optimization of PT in East Asia may include administration of PT after completed end-of-unit tests and a gradual change in feedback methodology over school years from test-oriented post-test lectures to the provision of literature references only, as a means of enhancing test self-review and self-directed learning.

Objective. To determine levels of interleukin 33 (IL-33) in serum and synovial fluid (SF) and their clinical associations in patients with rheumatoid arthritis (RA). To evaluate the ability of activated peripheral blood mononuclear cells (PBMC) and fibroblast-like synoviocytes (FLS) from RA patients to release IL-33. Methods. Sera were obtained from 59 patients with RA, 10 patients with infectious diseases, and 42 healthy volunteers. SF samples were obtained from 15 patients with RA and 13 with osteoarthritis. IL-33 levels were measured using a sandwich ELISA after removal of rheumatoid factor with protein A-Sepharose beads. FLS were stimulated with IL-1 beta and tumor necrosis factor, and treated with or without chemical damage. PBMC were stimulated with anti-CD3/CD28 antibodies. The levels of IL-33 were measured in the culture supernatants and cell lysates by ELISA or immunoblotting. Results. Serum IL-33 levels were significantly higher in RA patients, especially in the high disease activity group compared to the moderate or low activity group. IL-33 levels in SF were elevated in all 15 RA patients measured. IL-33 levels were higher in SF samples than in sera in 7 RA patients measured simultaneously. The 30-kDa IL-33 precursor was detected in the culture supernatants of damaged FLS but was not detected in those of activated PBMC and non-damaged FLS. Conclusion. IL-33 levels were elevated in sera and SF samples from patients with RA, and correlated with disease activity. IL-33 was produced mainly in inflamed joints; IL-33/ST2L signaling might play an important role in joint inflammation of human RA. (First Release Nov 15 2009; J Rheumatol 2010;37;18-25; doi:10.3899/jrheum.090492)

The objective of this study is to investigate the clinical markers of life-threatening Pneumocystis pneumonia (PCP) in patients with collagen vascular diseases (CVD). The patients who contracted Pneumocystis jeroveccii were retrospectively selected from our medical charts and conditions related to the patients' death were reviewed. The findings indicated that lower levels of serum albumin and cholinesterase, increased alveolar-arterial oxygen gradient, intratracheal intubation, and necessity to treat in the intensive care unit were significantly related to deaths associated with PCP in CVD. A special attention should be paid to decreased serum albumin and cholinesterase as ominous predictors in PCP occurred in patients with CVD.

Interleukin (IL)-33 is a novel member of the IL-1 family. IL-33 is primarily synthesized as a 30-kDa precursor (pro-IL-33). Pro-IL-33 is cleaved by caspase-1 into an 18-kDa mature form (mature IL-33) in vitro. Recombinant mature IL-33 has been known to induce T-helper type-2 (Th2)-associated cytokines and inflammatory cytokines via its receptor, ST2L However, processing of pro-IL-33 in vivo has not been clarified yet. Here, we report that calpain mediates pro-IL-33 processing in vivo. Pro-IL-33 was expressed by stimulating human epithelial cells with phorbol 12-myristate 13-acetate. Calcium ionophore induced pro-IL-33 cleavage and mature IL-33 production. This cleavage was inhibited by treatment with a calcium and calpain inhibitors. Moreover, short interfering RNA-mediated knockdown of calpains chelator suppressed pro-IL-33 cleavage. These results indicate that calpains play a critical role in pro-IL-33 processing in vivo. (C) 2009 Elsevier Inc. All rights reserved.

Protein-losing gastroenteropathy (PLGE) is a rare manifestation of primary Sjogren's syndrome (SS). We report a case of a 41-year-old Japanese man, who is the first male patient, with PLGE associated with primary SS. Although serum anti-SSA and SSB antibodies were detected, he had no subjective sicca symptoms. He had multiple annular erythema: a characteristic skin manifestation of Asian SS patients. A diagnosis of PLGE was made from results of Tc-99m-labelled albumin scintigraphy and a faecal alpha-1-antitrypsin clearance test. Intravenous administration of high-dose glucocorticoid was not effective, but pulse methylprednisolone therapy alleviated disease manifestations. As all cases of PLGE associated with primary SS have been reported from East Asia, this complication could be essentially limited to Asian patients.

We report a 29-year-old Japanese woman with disseminated intravascular coagulation (DIC) and adult onset Still&apos;s disease (AOSD). Her disease was refractory to high-dose glucocorticoids, two courses of steroid pulse therapy, and addition of cyclosporine (3.5 mg/kg/day). The serum interleukin-6 level was markedly elevated. Therefore, we administered an anti-interleukin-6 receptor antibody (tocilizumab, 8 mg/kg fortnightly), which dramatically improved her symptoms and the levels of acute-phase proteins. In addition, rapid tapering of the glucocorticoid dose was possible. Four months later, she was maintained on tocilizumab infusion once a month with low-dose steroid therapy. Cyclosporine is one of the first-line immunosuppressants for AOSD, especially when associated with DIC, hepatic failure, or hemophagocytic syndrome. In patients with cyclosporine-resistant AOSD, tocilizumab may be another useful option.

Problem: To investigate if systemic autoimmune diseases could be one of the risk factors for developing antisperm antibodies (ASA) in males. Method of study: Antisperm antibodies in the sera of 70 males with systemic autoimmune diseases and 80 healthy controls were examined, by using the indirect-immunobead test (I-IBT). The sperm immobilization test (SIT) was also performed to detect sperm immobilizing antibodies to the patients who were positive in I-IBT. Results: Among 70 males with systemic autoimmune diseases, five were I-IBT positives, with incidence of 7.1%. However, no positives existed in 80 healthy males. Compared with the healthy controls, the incidence of ASA in males with systemic autoimmune diseases was significantly higher (P = 0.020). None of these five ASA-positive patients had sperm immobilizing antibodies. Conclusion: The incidence of ASA in males with systemic autoimmune diseases was significantly higher than in the healthy controls. Systemic autoimmune diseases may be one of the risk factors for developing ASA in men. © 2009 John Wiley &amp Sons A/S.

We report two Japanese women with severe hepatic dysfunction and adult onset Still&apos;s disease. A 51-year-old woman had been diagnosed with adult onset Still&apos;s disease 3 years earlier. She relapsed while on maintenance therapy with prednisolone and methotrexate. After induction of remission with methylprednisolone pulse therapy, indomethacin, and methotrexate, severe hepatic failure occurred. This patient lacked the typical symptoms of adult onset Still&apos;s disease. The second patient was a 32-year-old woman with typical adult onset Still&apos;s disease. Remission was induced by high-dose prednisolone and methylprednisolone pulse therapy plus cyclosporine. After she stopped cyclosporine, severe liver dysfunction occurred. In both patients, liver dysfunction occurred during high-dose steroid therapy, and oral cyclosporine (3 mg/kg per day) dramatically improved their liver function. When steroid-resistant severe hepatic failure occurs in patients with adult onset Still&apos;s disease, cyclosporine may be the immunosuppressant of choice.

Systemic lupus erythematosus (SLE) is often complicated by pericarditis with effusion, which generally responds well to glucocorticoid. We report herein a Japanese patient with SLE who showed a sign of cardiac tamponade and severe chest and back pain because of massive intractable pericardial effusion. Pulse glucocorticoid and pulse cyclophosphamide gained marginal effects. Pericardial effusion accumulated again soon after ultrasound-guided pericardiocentesis and drainage. Pericardial fenestration performed Surgically as a last resort, for draining pericardial fluid into the pleural space, was very effective, and only a much smaller amount of fluid was observed in the space thereafter in comparison with the volume before the surgery. Pathological examination of the retrieved pericardium unfolded intense hyperplasia of small vessels and capillaries. Levels of IL-6 and TNF-alpha in pericardial effusion were extremely higher than those in serum. Pericardial effusion with extensive capillary hyperplasia in SLE would be resistant to medical treatment and require surgical fenestration. Lupus (2008) 17, 1033-1035.

Objective. CD34-positive bone marrow mononuclear cells (MNCs) have been successfully used for regeneration of small arteries in Buerger's disease. The objective of this study is to examine the angiogenetic potential of autologous MNCs from bone marrow and peripheral blood implanted into the ischaemic digits from patients with connective tissue diseases. Methods. Three patients with systemic sclerosis, two with mixed connective tissue disease, and one with CREST syndrome were enrolled who had painful ischaemic digits with necrosis refractory to several vasodilators including intravenous prostaglandins. MNCs obtained from 7 ml/kg bone marrow blood and 400 ml peripheral blood were implanted into 20 different sites in palms and/or soles. The study was performed open-labelled. Results. Pain in the numeric rating scale improved remarkably up to 1 month after implantation of bone marrow or peripheral MNCs to the same extent, although no significant differences were found in transcutaneous oxygen pressure and thermogram before and after the implantation. Bone marrow MNCs increased blood flow of the hand determined by intra-arterial digital subtraction angiography, while peripheral MNCs did not. Conclusions. Implantation of autologous MNCs from peripheral and bone marrow into the ischaemic digits was so effective in pain-relief and more clinical trials would be warranted to see whether this could be a new treatment modality for angiogenesis in connective tissue diseases as in Buerger's disease. © The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Objective. To determine whether statins induce apoptosis in rheumatoid arthritis (RA) synoviocytes. Methods. The effects of lipophilic and hydrophilic statins (fluvastatin and pravastatin, respectively) on the apoptosis of cultured RA synoviocytes were examined in vitro. Apoptosis was analyzed by flow cytometry after staining with JC-1 (to measure the mitochondrial transmembrane potential), active caspase 3, annexin V, and propidium iodide. Add-back experiments were conducted to determine which downstream products of the mevalonate pathway could suppress apoptosis. Modulation of various signaling pathways induced by statins, including protein prenylation, was also investigated. Results. Fluvastatin, but not pravastatin, induced apoptosis in RA synoviocytes in a concentration-dependent (1-10 μM) and time-dependent (48-96 hours) manner. Another lipophilic statin, pitavastatin, displayed almost the same effects as fluvastatin. In sharp contrast, lipophilic statins did not significantly increase apoptosis in synoviocytes from patients with osteoarthropathy. Apoptosis induced by fluvastatin was mitochondrial- and caspase 3-dependent and was abrogated by mevalonate and geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate. In addition, the geranylgeranyl transferase inhibitor GGTI-298 mimicked the effect of fluvastatin on RA synoviocytes. Treatment of RA synoviocytes with the RhoA kinase inhibitor Y-27632 caused apoptosis. Fluvastatin decreased the amount of RhoA protein in the membrane fraction, but increased the amount in the cytosolic fraction. Conclusion. Fluvastatin induced apoptosis in RA synoviocytes through a mitochondrial- and caspase 3-dependent pathway and by the blockage of mevalonate pathways, particularly through the inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathways. These findings suggest that lipophilic statins have potential as novel therapeutic agents for RA. © 2006, American College of Rheumatology.

A 70-year-old man presenting with a chief complaint of tongue swelling had been diagnosed with prostate cancer 1 year earlier. He had been on an oral angiotensin-converting enzyme inhibitor (ACE) inhibitor for hypertension for 20 years. Two months before the first of 4 episodes of tongue swelling within a period of 40 days, he had been prescribed oral estramustine phosphate (EMP) for the prostate cancer. He was admitted to our hospital for the evaluation after massive swelling of the tongue and epiglottis which necessitated tracheotomy. Food allergies, allergic reactions to environmental factors, and hereditary angioneurotic edema were excluded. Massive swelling of the tongue and epiglottis disappeared completely after EMP was discontinued. We concluded that angioedema was induced by EMP used concurrently with the ACE inhibitor. © 2006 Esmon Publicidad.

A 74-year-old woman with Sjögren's syndrome and chronic hepatitis C (CHC) was admitted to our hospital in October 2003 for treatment of diabetes mellitus. She had the past history of recurrent thrombocytopenia, which was proven to be due to peripheral destruction. Although she had been diagnosed with hypertrophic cardiomyopathy (HCM) for 2 years, she had never felt palpitation. She suddenly died probably of fatal arrhythmia related to HCM during the last hospitalization. Although hepatitis C virus (HCV) infection has been associated with Sjögren's syndrome, thrombocytopenia, HCM, and diabetes mellitus, all these diseases rarely occur in a single patient. It will be necessary to identify similar cases to elucidate the etiopathogenesis of extrahepatic manifestations of HCV infection.

A 26-year-old woman presented with high fever, marked supraclavicular lymphadenopathy, and morbilliform eruptions and was diagnosed with Kikuchi's disease (KD) based on pathologic findings from biopsied lymph nodes. All her manifestations of KD improved, however, without any specific treatment. The picture of transient morbilliform eruptions typified in KD here is seldom shown in the literature. In general, KD would run a benign course of supraclavicular lymphadenopathy. © Springer-Verlag 2004.

Infliximab was introduced along with methotrexate 8mg/week to a female patient with intractable rheumatoid arthritis. Although a dramatic improvement of her arthritic symptoms was achieved immediately, a small nodular shadow developed in the right middle field of her lung, visible on chest X-ray at the third injection. Because the nodular shadow rapidly increased its size in a week, transbronchial fiberoptic examination was performed and lavage fluid was obtained. The polymerase chain reaction was positive for Mycobacterium avium and the bacterial growth in culture confirmed the diagnosis. Although tuberculosis is a well-known adverse reaction to infliximab, development of nontuberculous mycobacteriosis is quite rare and no such report has so far been published in the context of infliximab usage. We should be alert to the fact that nontuberculous mycobacteriosis of slow progression in a usual clinical setting progresses quite rapidly, thus treatment should not be delayed, especially in patients on infliximab. © Japan College of Rheumatology and Springer-Verlag Tokyo 2005.

Two different bacterial strains with different drug susceptibilities were isolated from the sputum and an inflammatory discharge from a swelling in the left thigh of a patient with rheumatoid arthritis. Both bacterial strains were provisionally assigned to the genus Nocardia on the basis of their morphological and chemotaxonomic characteristics and were further studied in order to establish their taxonomic status. One strain (IFM 10034) was identified as Nocardia farcinica on the basis of its physiological characteristics. The other strain, which was designated Nocardia sp. strain IFM 10035T, revealed a unique pattern of phenotypic properties that distinguished it from other representatives of established Nocardia species. Comparative 16S rRNA gene sequence studies of Nocardia sp. strain IFM 10035 T also showed that the bacterium was closely related to the species Nocardia beijingensis. Determination of DNA-DNA relatedness, however, indicated that Nocardia sp. strain IFM 10035T could be delineated from N. beijingensis. The genotypic and phenotypic data combined indicated that the bacterium merits description as a new Nocardia species. The name proposed for the new species is Nocardia arthritidis sp. nov., the type strain being IFM 10035T (NBRC 100137T, JCM 12120T, DSM44731 T). The present study suggests that Nocardia infections can be caused by multiple species of the bacterium.

HMG-CoA (3-hydroxy-3-methyglutaryl coenzyme A) reductase inhibitors (statins) reduce cardiovascular morbidity and mortality. Although statins work in part via lipid modulation, several findings of statins indicate they have broader properties, including alteration of inflammatory pathways. Ex-vivo activities of statins include suppression of adhesion molecule expression, MHC class II expression, and effects on reactive oxygen and nitrogen intermediate production. Statins also modify apoptosis in smooth muscle and endothelial cells leading to altered vascular function and neovascularization. These properties offer the potential to modify the states of chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis with drugs that show minimal toxic effects in both the short and long term. © 2004, The Japan Society for Clinical Immunology. All rights reserved.

Objective. To examine the role of immune complexes in the prostanoid metabolism of glomerular capillary endothelial cells (EC) and platelets in lupus nephritis. Heat aggregated IgG (HA-IgG), instead of immune complexes, was incubated using an in vitro coculture system with human umbilical vein EC, instead of glomerular capillary EC, and platelets. The effect of complement component C1q and a novel imidazole-type thromboxane A(2) (TXA(2)) synthetase inhibitor, DP-1904, on this prostanoid metabolism change was also investigated. Methods. EC monolayers (1.5 x 10(5) cells/well) were incubated with various concentrations of HA-IgG, monomeric IgG, or medium alone for 1 h at 37degreesC, and then incubated with platelet suspensions (1 x 10(8) cells/ml) for various times. Concentrations of TXB2 and 6-keto-prostaglandin F-1alpha (6-keto-PGF(1alpha)), the stable hydrolysis products of TXA(2) and prostaglandin I-2 (PGI(2)), respectively, released in the supernatants were measured by ELISA. Results. HA-IgG bound to EC monolayers produced TXB2 and 6-keto-PGF(1alpha) in a concentration dependent manner and much more than monomeric IgG or medium alone did. However, the production of 6-keto-PGF(1alpha) stimulated with HA-IgG was much lower than that of TXB2, indicating a large imbalance between TXA(2) and PGI(2). Preincubation of HA-IgG with purified C1q partially suppressed the production of TXB2, but not that of 6-keto-PGF(1alpha). DP-1904 suppressed the production of TXB2 completely, but by sharp contrast, it dramatically increased the production of 6-ketoPGF(1alpha) from EC and platelets by HA-IgG. Conclusion. The large imbalance of TXA(2) and PGI(2) produced by the interaction of EC, immune complexes, and platelets may be associated with alterations in glomerular pathological findings and hemodynamics mediated by immune complexes in lupus nephritis. C1q and a TXA(2) synthetase inhibitor may improve the abnormal prostanoid metabolism change of lupus nephritis.

Background Th2 and Th1 cells have been suggested to express CCR3/CCR4 and CCR5/CXCR3, respectively. Objective We examined CCR3, CCR4, CCR5 and CXCR3 expression and cytokine production in peripheral blood CD4(+) T cells from patients with atopic dermatitis (AD), which has been postulated to be a Th2-type cell-mediated disease, and then analysed the possible correlation between these values and the levels of several clinical parameters. Methods Intracellular cytokine production and chemokine receptor expression in peripheral blood CD4(+) T cells from 40 AD patients and 20 sex- and age-matched healthy control subjects were studied by flow cytometry. Results The frequencies of IL-4- and IL-13-producing CD4(+) T cells from patients with AD were significantly higher than those from healthy control subjects (IL-4:3.9 +/- 2.1% vs. 1.6 +/- 0.7%, P = 0.0005, IL-13:4.0 +/- 2.1% vs. 1.8 +/- 0.8%, P = 0.0023), whereas the frequencies of IL-2- and IFN-gamma-producing CD4 (+) T cells were significantly decreased in AD patients (IL-2:38.1 +/- 10.3% vs. 51.3 +/- 6.3%, P = 0.0003, IFN-gamma: 9.9 +/- 3.5% vs. 26.4 +/- 4.6%, P &lt; 0.0001). The percentage of CCR4 (+) cells in CD4(+) CD45RO (+) T cells in AD patients was significantly higher than that in healthy control subjects (24.4 +/- 8.0% vs. 10.9 +/- 2.3%, P &lt; 0.0001) and was correlated positively with the total serum IgE, serum lactic dehydrogenase (LDH) level, eosinophil number, eruption score, and IL-4 and IL-13 secretion in CD4 (+) T cells, and inversely with IL-2 and IFN-gamma secretion in CD4(+) T cells. In contrast, CCR3 was not detected on circulating CD4(+) T cells even in AD patients. On the other hand, the percentage of CCR5(+) or CXCR3 (+) cells in CD4(+) CD45RO(+) T cells in AD patients was significantly decreased (CCR5:23.2 +/- 7.0% vs. 28.4 +/- 5.4%, P = 0.023, CXCR3:29.9 +/- 11.4% vs. 38.5 +/- 6.7%, P = 0.028) and was positively correlated with eruption score (P &lt; 0.05). Multiple regression analyses showed that the percentage of CCR4 expression highly correlated with serum IgE, LDH, eosinophil number and eruption in AD patients. Conclusion CCR4(+) cells might be involved in the aetiopathogenesis of AD.

A 17-year-old girl had been placed with ventriculoperitoneal, then ventriculoatrial shunts for congenital hydrocephalus since birth. The patient originally was diagnosed as having a lupus like disease, but later turned out to have shunt nephritis, presenting with fever, proteinuria, pancytopenia, and hypocomplementemia. Antineutrophil cytoplasmic autoantibody specific for proteinase 3 (PR3-ANCA) was detected in her serum. The patient received oral prednisolone and repeated methylprednisolone pulses, with essentially no beneficial affects. A gram positive coccus, Gemella morbillorum, was recovered from her blood as well as cerebrospinal fluid, and the culture of the shunt catheter established the diagnosis of shunt nephritis. Removal of the shunt catheter improved symptoms dramatically and decreased PR3-ANCA in serum to an undetectable level. Because steroids had no effects and the control of bacterial infection lowered PR3-ANCA levels, the antibody would have been induced by continuous infection with G morbillorum. (C) 2001 by the National Kidney Foundation, Inc.

To elucidate the autoantigen against which autoantibodies are produced in the earliest phase of the disease:process of systemic lupus erythematosus (SLE), serum samples were collected individually and serially from 10 NZB/NZW F1 and 10 MRL/lpr mice. Using immunoblots with mouse thymoma cell (EL-4) lysates as substrates, all mice were found to generate autoantibody against an either 150-kDa, 110-kDa, 75-kDa, or 55 kDa molecule in as early as 4 weeks. Anti-DNA antibodies occurred almost at the same time or after those against these four molecules. The number of antigens reactive with autoantibodies in immunoblots increased gradually with age. Antibodies against histone molecules were produced after 8 weeks of age. Among the four antigens, the 110-kDa molecule was identified as nucleolin, which is an abundant nucleolar phosphoprotein. Nucleolin binds DNA, RNA, and nucleic acid-binding proteins such as histone H1. Nucleolin is a target of granzyme A of cytotoxic T cells, and autoantibodies against it are found in sera from patients with SLE as well as from those with various viral infections. These results indicate that nucleolin is one of the immunodominant molecules that break down self-tolerance and initiate autoantibody-spreading in a mouse model of SLE. (C) 2000 Academic Press.

Objective, To determine whether there is a close temporal relationship of liver disease to serum IgG and/or IgM antiribosomal PO protein antibodies (anti-PO) and central nervous system (CNS) lupus in patients with systemic lupus erythematosus (SLE). Methods. The study included 70 patients with active SLE. Of these, 30 had IgG and/or IgM anti-PO and 14 had CNS lupus other than psychiatric disease (nonpsychiatric CNS lupus). Of these 14 patients, 11 had anti-PO. Laboratory manifestations of liver disease were retrospectively analyzed. Results, Liver disease not attributed to any cause other than SLE (SLE liver disease) was present in 8 of the 11 patients with anti-PO with nonpsychiatric CNS lupus (72.7%), in none of the 19 patients with anti-PO without nonpsychiatric CNS lupus (0%), and in one of the 40 patients without anti-PO (2.5%). The prevalence of SLE liver disease was significantly greater in patients with anti-PO with nonpsychiatric CNS lupus than in the other 2 groups (p &lt; 0.0001). Mean levels of liver enzymes (lactate dehydrogenase, glutamic oxaloacetic transaminase, glutamate pyruvate transaminase, gamma-glutamyl transpeptidase) were significantly higher in patients with anti-PO with nonpsychiatric CNS lupus than in the other 2 groups. Serial studies in 3 patients showed that the appearance of anti-PO and liver dysfunction slightly preceded the onset of nonpsychiatric CNS lupus. Conclusion, Anti-PO may be related to the pathogenesis of CNS lupus and SLE liver disease found simultaneously in SLE. The appearance of anti-PO and liver dysfunction may predict onset of CNS lupus.