The Japanese LupusPRO: A cross-cultural validation of an outcome measure for lupus.

Objective This study aimed to validate the Japanese version of the LupusPRO questionnaire for use with systemic lupus erythematosus patients. Methods Participants were 205 lupus patients recruited from three rheumatology centers in Japan. Demographic data were collected and quality of life was assessed using the LupusPRO and the Short Form Health Survey-12. Disease activity was evaluated by physicians using the Systemic Lupus Erythematosus Activity Index. Some participants completed questionnaires 10-14 days after the first survey. Internal consistency reliability, test-retest reliability, content validity and convergent validity were examined, and confirmatory factor analysis was performed. Results Participants' mean age was 47.8 ± 13.6 years. Older participants scored lower on physical quality of life and higher on coping than younger participants. The LupusPRO showed satisfactory test-retest reliability ( n = 111). Test-retest reliability was lower for the mental and social aspects of quality of life, indicating fluctuations in quality of life during the two-week interval. Internal consistency reliability was good and convergent validity with the corresponding domains of the Short Form Health Survey-12 was satisfactory. Confirmatory factor analysis showed a good model fit. Conclusion The Japanese LupusPRO is a reliable and valid measure to evaluate treatment interventions for systemic lupus erythematosus.

Effects of high-monounsaturated fatty acid enteral formula versus high-carbohydrate enteral formula on plasma glucose concentration and insulin secretion in healthy individuals and diabetic patients.

We investigated the effects of high-monounsaturated fatty acid (MUFA) versus high-carbohydrate enteral formula on post-prandial plasma glucose concentration and insulin response in Japanese patients with type 2 diabetes mellitus and healthy Japanese volunteers. Ten healthy volunteers aged 20.8 +/- 1.2 years and 12 diabetic patients with good glycaemic control (glycosylated haemoglobulin < 7%) aged 58.6 +/- 7.7 years were randomly assigned to take high-MUFA or high-carbohydrate formula after a 12-h overnight fast. The patients switched to the other formula after 7 days. Post-prandial plasma glucose and insulin response were significantly lower in all subjects after taking high-MUFA formula compared with high-carbohydrate formula. No differences were observed in free fatty acids, triglycerides and plasma glucagon between the two diet groups. In conclusion, a high-MUFA enteral formula suppresses post-prandial hyperglycaemia without exaggerated insulin secretion compared with a high-carbohydrate enteral diet in patients with type 2 diabetes and healthy subjects.

Predictors of poor sleep quality in patients with systemic lupus erythematosus.

Sleep problems are common in patients with systemic lupus erythematosus (SLE). This study aimed to examine the following: (1) predictors of sleep quality and (2) fluctuations in sleep quality in patients with SLE. Patients with SLE were recruited from three rheumatology centers in Japan. We collected demographic and clinical data and data on sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI), the Medical Outcome Study Short Form-12, and the Lupus Patient Reported Outcome Tool (LupusPRO). Fluctuations in sleep quality were examined by administering the PSQI a second time after a 2-week interval. We used multiple linear regression analysis to predict sleep quality. Of 205 patients who completed the survey, 62.9% showed poor sleep quality. The largest fluctuation in sleep quality was for "waking in the middle of the night or early morning." "LupusPRO pain/vitality" was a major predictor of poor sleep. The other significant predictors were mostly LupusPRO subscales and clinical variables and SF-12 subscales were mostly non-predictive. The majority of the participants had poor sleep quality. A lupus-specific QoL scale is important for understanding poor sleep quality in SLE patients. Symptom management appeared to play a key role in improving sleep quality.

Design and synthesis of a more highly selective ammonium ionophore than nonactin and its application as an ion-sensing component for an ion-selective electrode

A novel ammonium ionophore, which exhibits superior NH4+ selectivity compared with that of the natural antibiotic nonactin, was successfully designed and synthesized based on a 19-membered crown compound (TD19C6) having three decalino subunits in the macrocyclic system. This bulky decalino subunit is effective for (1) increasing the structural rigidity of the cyclic compound, (2) introducing the "block-wall effect", which prevents forming a complex with a large ion, and (3) increasing the lipophilicity of the ionophore molecule. In the ammonium ionophore design, the first factor contributes to increasing the NH4+ selectivity relative to smaller ions such as Li+, Na+, or even the closest size, K+, and the second factor increases the NH4+ selectivity over larger ions such as Rb+ and Cs+. The X-ray structural analysis proved that TD19C6 forms a size-fit complexwith NH4+ in its crown ring cavity. As an application of this ionophore, an ion sensor (ion-selective electrode) was prepared, which exhibited NH4+ to K+ and Na+ selectivity of 10 and 3,000 times, respectively. This electrode showed a better performance compared to the electrode based on nonactin, which is the only ammonium ionophore presently used in practical applications.

[A case of miliary tuberculosis (miliary TB) accompanied with adult respiratory distress syndrome (ARDS) in a patient with Cushing's syndrome].

A 74-year-old housewife was admitted to the hospital with complaints of high fever and general fatigue. The physical examinations on admission showed no particular findings except for mild hepatomegaly, but laboratory findings showed severe liver dysfunction, active inflammation and negative tuberculine test. On the 4th day, she suddenly complained of severe respiratory distress. A chest X-ray film demonstrated surprising changes in comparison with that taken on admission. On suspicion of adult respiratory distress syndrome (ARDS) associated with military tuberculosis (Miliary TB), administration of Methylpredonisolone (1000 mg a day for 3 days) in addition to antituberculous drugs was immediately started. With this therapy she was recovered from such ill condition, but the general exhaustion and slight fever continued. We suspected that her condition might be due to adrenocortical involvement of Miliary TB and hormonal examinations were performed. Unexpectedly, Cushing's syndrome was suspected on the basis of the following; high level of plasma cortisol without normal daily variation, normal ACTH level, an absent response to the Dexamethasone suppression test. Computed tomography revealed left side adrenal mass. During these examinations, renal dysfunction probably due to Miliary TB grew gradually worse and she died of renal failure on the 56th day. Necropsy revealed disseminated tuberculosis involving the lungs and the liver, but the adrenal glands were not examined.

[A case of agranulocytosis and jaundice due to cellulitis caused by insect bite].

A 58-year-old female was introduced to our hospital for admission on April 22, 1988, because of high grade fever and agranulocytosis. She had eschers on her left zygomatic region and medial region of the right thigh. The latter lesion was accompanied by cellulitis. Laboratory tests showed her WBC was 600/mm3 and T-Bil was 6.51 mg/dl. By using minocyclin, piperacillin and other drugs, her general condition and laboratory data became better in a few days. Although her skin lesions resembled "Tsutsugamushi disease", serological tests showed no evidence for Rickettia infection. So we could not rule out that another kind of insect bite may also develop such a severe clinical course. Furthermore, Staphylococcus aureus or Clostridium spp., which were detected in her pus, might have the toxic effects of inducing agranulocytosis, which might mainly be the result from the local WBC emigration, and jaundice, just like the effects of the endotoxin of Gram negative bacteria.

Gamma interferon is produced by human natural killer cells but not T cells during Staphylococcus aureus stimulation.

Gamma interferon (IFN-gamma) production from cultured human peripheral blood mononuclear cells was studied during stimulation with Staphylococcus aureus Cowan I or S. aureus Wood. IFN-gamma was specifically produced from CD16+ natural killer (NK) cells under stimulation by S. aureus Cowan I or Wood because these strains (i) induced IFN-gamma production exclusively from CD3-, CD4- CD8-, and CD16+ cells and (ii) induced CD69 and interleukin 2 (IL-2) receptor alpha expression on CD16+ cells without simultaneously augmenting CD71 or IL-2 receptor alpha on T cells. The effects of biological agents on the induction of S. aureus-induced IFN-gamma production paralleled those of S. aureus-induced CD69 expression on CD16+ cells: IL-2, IFN-alpha, and indomethacin augmented the S. aureus-induced IFN-gamma production, whereas IL-4, transforming growth factor beta 1, prostaglandin E2, and dexamethasone inhibited it. However, IFN-alpha was unique in that it did not induce IFN-gamma production from NK cells while it simultaneously augmented CD69 expression on NK cells, suggesting a unique pathway in the activation of NK cells. Thus, we may conclude that S. aureus-induced IFN-gamma production appears to faithfully represent NK cell function within peripheral blood mononuclear cells.

The contribution of human c-fos DNA to cultured synovial cells: a transfection study.

To clarify the role of c-fos DNA in the activation of human synovial cells, the pH8 expression vector containing human c-fos DNA under the control of murine leukemia virus long terminal repeat was transfected into cultured synovial cells. After G418 selection, the control transfectant clones transfected with pH8 vector not containing c-fos DNA insertion changed their original fibroblastic shape into dendritic cells. They stopped growing at this stage. However, the c-fos DNA transfectant clones continued to grow actively beyond this stage, and regained the fibroblastic appearance. Furthermore, c-fos DNA transfectants adhered to and grew on hyaluronidase treated cartilage surfaces more extensively than control transfectants after 6 days in culture. These findings suggest that c-fos DNA supports active growth of human synovial cells by facilitating transition of synovial dendritic cells into fibroblastic cells.

Tumor necrosis factor alpha and interferon gamma inhibit proliferation and alkaline phosphatase activity of human osteoblastic SaOS-2 cell line.

Tumor necrosis factor (TNF) alpha and TNF beta both inhibited proliferation of cultured human osteoblastic SaOS-2 cells. TNF alpha also inhibited alkaline phosphatase (ALP) activity in the cells. The TNF alpha-induced inhibition of proliferation and ALP activity was further potentiated by interferon (IFN) gamma. These findings indicate that human SaOS-2 cells, fulfilling several criteria for osteoblasts, respond to TNF alpha and IFN gamma, resulting in decceleration of their maturation.

Pathogenic importance of fibronectin in the superficial region of articular cartilage as a local factor for the induction of pannus extension on rheumatoid articular cartilage.

To identify the local factors in cartilage that are responsible for the induction of pannus invasion, a 14 day organ culture study in which rheumatoid synovium was grown in contact with cartilage pieces was carried out. Rheumatoid synovium preferentially extended over hyaluronidase treated cartilage pieces, but detached from untreated pieces. Rheumatoid synovium extended over hyaluronidase treated cartilage surfaces containing fibronectin more extensively than over surfaces treated with hyaluronidase only. Extension over hyaluronidase treated cartilage surfaces containing immune complexes was small. The adherence of synovial cells to hyaluronidase treated cartilage slices in vitro was specifically inhibited by the synthetic peptide, Gly-Arg-Gly-Asp-Ser-Pro, which is the adhesive portion of the fibronectin molecule. Furthermore, synovial fibroblast-like cellular extension, morphologically similar to rheumatoid pannus, was observed in the organ culture experiments in which rheumatoid synovium grew over hyaluronidase treated cartilage surfaces containing fibronectin. Synovial tissue extension over fibronectin coated surfaces was inhibited when hyaluronic acid and chondroitin-4-sulphate, major components of cartilage proteoglycans, were present on the cartilage surface. These findings suggest that fibronectin present in the superficial region of cartilage potentiates rheumatoid synovial extension and proteoglycans and immune complexes inhibit rheumatoid synovial extension. It is likely that fibronectin deposited on the eroded surface of articular cartilage induces pannus formation in rheumatoid arthritis.

[Rapidly progressive glomerulonephritis associated with myeloperoxidase specific-antineutrophil cytoplasmic antibody in patients with rheumatoid arthritis : report of three cases].

The reports on the patients with rheumatoid arthritis (RA) complicated with the myeloperoxidase specific-antineutrophil cytoplasmic antibody (MPO-ANCA) associated glomerulonephritis, whose clinical feature is rapidly progressive glomerulonephritis (RPGN), have been rare. We here report three cases of RPGN with MPO-ANCA in RA patients. Case 1. A 44-year-old woman with RA for 25 years was admitted because of RPGN. The level of MPO-ANCA was markedly high (293 EU) and the histological examination of the kidney showed diffuse crescentic glomerulonephritis. In spite of the intensive immunosuppressive therapy, her renal function did not recover and she underwent hemodialysis (HD). Case 2. A 58-year-old man with RA for 5 years was admitted due to RPGN (MPO-ANCA ; 147 EU, Ccr ; 16 ml/min) with the nephrotic syndrome and fever. The treatment with the immunosuppressive agents and the plasma exchange was partially effective to stop the rapid progression of the disease, but a few months later, his renal function worsened (Ccr 7 ml/min). A recent histological examination of the kidney failed to establish the CrGN because of endstage kidney. Case 3. A 56-year-old woman with RA for the past 10 years was admitted because of RPGN (MPO-ANCA ; 652EU). Intensive therapy could not be performed because of an active duodenal ulcer and markedly impaired renal function (Ccr ; 6 ml/min), and soon she underwent HD. Renal biopsy was not done. These three cases suggest that RPGN can occur in part of RA patients with MPO-ANCA.

Effects of interaction of tannins with co-existing substances. VII. Inhibitory effects of tannins and related polyphenols on xanthine oxidase.

The inhibitory effects of hydrolyzable tannins, condensed tannins and related polyphenols on the activity of xanthine oxidase (XOD), catalyzing uric acid formation from xanthine, were investigated. Marked differences in the strength of the inhibition were observed. Some of the differences among the monomeric hydrolyzable tannins were due to their molecular weights, reflecting the number of phenolic hydroxyl groups in the molecule. However, the inhibitory activity of several oligomeric hydrolyzable tannins seemed particularly low in spite of their large molecular size. It was also observed that differences in location of acyl groups on the carbohydrate cores caused differences in the inhibitory activity among monomeric and oligomeric hydrolyzable tannins. A caffeic acid derivative (caffeetannin), 3,5-di-O-caffeoylquinic acid (24), also inhibited this enzyme. Galloylation and the degree of polymerization in proanthocyanidins were also shown to affect remarkably the strength of the inhibition. Among the compounds tested in the present study, valoneic acid dilactone (29), isolated from Mallotus japonicus, inhibited the enzyme most effectively. A kinetic study showed that this dilactone inhibited XOD non-competitively. Comparison of the inhibitory effect on XOD, with the binding activity to hemoglobin, for each tannin, suggests that their inhibition of XOD is not based on non-specific binding to the protein. Similar comparison of the inhibitory effect on XOD with the inhibitory effect on the generation of superoxide anion radical (O2-.) from the hypoxanthine-XOD system revealed that the inhibition of O2-. generation by tannins is due to their radical-scavenging activity, and not due to their inhibitory activity upon the enzyme.

Immunoreactive circulating alpha-interferon is low in Sjögren's syndrome.

Circulating alpha-interferon in plasma of 26 patients with Sjögren's syndrome was 0.069 +/- 0.034 ng/ml, a significant decrease compared with 0.119 +/- 0.051 ng/ml for age- and sex-matched healthy subjects (P less than 0.01) and compared with values previously found for healthy donors at ages 1-89 years. The results indicate the inability of Sjögren's syndrome patients to maintain circulating alpha-interferon.

Age distribution of circulating alpha-interferon.

A sensitive radioimmunoassay showed that circulating alpha-interferon in the plasma of healthy individuals was low in children and reached the highest level in the young adult, then declined gradually with age. Circulating alpha-interferon was 0.201 +/- 0.059 ng/ml in males (n = 19) and 0.184 +/- 0.076 ng/ml in females (n = 14) at ages 30-39 years old. It was noted that circulating alpha-interferon was maintained up to a certain level even in elderly individuals.