Serum level of soluble urokinase plasminogen activator receptor (suPAR) as a disease severity marker of myasthenia gravis: a pilot study.

Myasthenia gravis (MG) is an autoantibody-mediated inflammatory disease of the neuromuscular junction. Biomarkers indicating disease activity in MG are warranted. Recently, the soluble urokinase plasminogen activator receptor (suPAR) has been reported to be associated with inflammation, tissue damage, disease activity and prognosis in various diseases, including autoimmune diseases. In this study, serum suPAR levels were measured in 40 patients with anti-acetylcholine receptor antibody-positive MG and 30 controls, and their correlations with clinical variables and severity scale scores were investigated. We identified that serum suPAR levels significantly correlated with MG activities of daily living scale (Spearman's ρ = 0·45; P = 0·004) and MG Foundation of America classification (Spearman's ρ = 0·37; P = 0·02) at serum sampling, but not with anti-acetylcholine receptor antibody titers. In conclusion, serum suPAR levels can be a candidate for a novel biomarker of disease activity in anti-acetylcholine receptor antibody-positive MG.

SU-E-I-21: Effect of Different Fluorescent Lights with Various Colors of a Reading Room on Chromaticity of LCD.

PURPOSE: To examine variation of chromaticity of LCD in different types of fluorescent lights in a reading room. METHODS: A color LCD (RX320, antiglare type, 450 cd/m2 , three-megapixel, Eizo Nanao), and a monochrome LCD (G31-S, anti glare type, 450 cd/m2 , three-megapixel, Eizo Nanao) were used in this study. The chromaticity in grayscale images with eighteen luminance levels were measured under five types of fluorescent lights with different color spectrums (Daylight: 6,700 K, Natural white: 5,000 K, White: 4,200 K, Warm white: 3,500 K, Light bulb: 3,000 K) by using a colorimeter (CS-200: KONICA MINOLTA). The chromaticity of LCDs was measured at various ambient lighting conditions (a dark room, 36, and 300 lux) and different types of fluorescent lights. RESULTS: The chromaticity of LCDs measured under ambient lights was changed from that measured in a dark room. The chromaticity of LCDs varied with different types of fluorescent lights. As illuminance of the room increased, variations in chromaticity at relatively lower luminance levels increased. The direction of changes in chromaticity shifted to the color for each fluorescent light. CONCLUSIONS: Fluorescent lights having different color spectra affect the chromaticity of LCDs.

Influence of nitrogen fertilization on tropical-grass silage assessed by ensiling process monitoring using chemical and microbial community analyses.

AIMS: Utilization of silage in livestock farming is expected to increase in developing countries in the tropical and subtropical parts of the world. The aim of this study was to investigate the influence of nitrogen fertilization on the chemical composition of herbage, ensiling process and silage quality, and to contribute to the improvement of tropical-grass silage preparation. METHODS AND RESULTS: Guinea grass grown under two different nitrogen-fertilizer application conditions [1.5 kg N a(-1) (high-N) and 0.5 kg N a(-1) (low-N)] was packed in plastic bags, and its ensiling process was investigated by chemical and microbial-community analyses. Relatively well-preserved silage was obtained from high-N herbage, which accumulated a high nitrate concentration. Denaturing gradient gel electrophoresis analysis revealed that Lactobacillus plantarum dominated throughout the ensiling of high-N herbage and in the early phase of that of low-N herbage. In low-N silages prepared from ammonium sulfate- and urea-fertilized herbage, Lact. plantarum was replaced by clostridia after 40 and 15 days of ensiling, respectively. CONCLUSIONS: Nitrate content of herbage is an important factor that influences silage quality, and careful fertilization management can facilitate stable and successful fermentation of tropical-grass silage without any pretreatment. SIGNIFICANCE AND IMPACT OF THE STUDY: The positive effect of nitrate on the ensiling process of tropical-grass was proved by microbial-community analysis.

Therapeutic efficacy of sustained drug release from chitosan gel on local inflammation.

The model anti-inflammatory drug prednisolone (PS) was retained in chitosan (CS) gel beads, which were prepared in a 10% aqueous amino acid solution (pH 9.0). Sustained release of PS from the CS gel beads was observed. Carrageenan solution was injected into air pouches (AP), which were prepared subcutaneously on the dorsal surface of mice, in order to induce local inflammation. CS gel beads retaining PS were then implanted into the AP to investigate the therapeutic efficacy of sustained PS release against local inflammation. In vivo PS release from CS gel beads was governed by both diffusion of the drug and degradation of the gel matrix. Sustained drug release by CS gel beads allowed the supply of the minimum effective dose and facilitated prolonged periods of local drug presence. Inflammation indexes were significantly reduced after implantation of CS gel beads when compared with injection of PS suspension. Thus, extension of the duration of drug activity by CS gel beads resulted in improved therapeutic efficacy. These observations indicate that CS gel beads are a promising biocompatible and biodegradable vehicle for treatment of local inflammation.

Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease.

OBJECTIVE: We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population. RESEARCH DESIGN AND METHODS: We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset <30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects. CONCLUSIONS: An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this apanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism.

Urinary iodine and thyroid antibodies in Okinawa, Yamagata, Hyogo, and Nagano, Japan: the differences in iodine intake do not affect thyroid antibody positivity.

Excess iodine intake may affect the development of Hashimoto's thyroiditis. Kelp consumption is very high in Okinawa. We expected a high prevalence of Hashimoto's thyroiditis in Okinawa. We studied urinary iodine excretion and the positivities of anti-thyroglobulin antibodies (TGAb) and anti-thyroid peroxidase antibodies (TPOAb) in the residents of Nishihara in Okinawa, Yamagata in Yamagata, Kobe in Hyogo, and Hotaka in Nagano, Japan. TGAb and/or TPOAb were positive in 142 (13.7%) of 1039 subjects in Nishihara, in 16 (16.0%) of 100 subjects in Yamagata, in 31 (13.4%) of 232 subjects in Kobe, and in 35 (13.9%) of 252 subjects in Hotaka; TGAb and/or TPOAb positivity was about the same in these 4 areas. One tenth of the subjects with positive TGAb and/or TPOAb had hypothyroidism; the frequencies of hypothyroidism in those with positive TGAb and/or TPOAb were about the same in Nishihara, Yamagata, Kobe, and Hotaka. The iodine concentration in samples of morning urine correlated well with the 24-h urine iodine excretion. The urinary iodine excretion was 1.5 mg/day in Nishihara. There were no differences between Nishihara and Yamagata in the urinary iodine concentration, but the urinary iodine concentrations in Kobe and Hotaka were less than those in Nishihara or Yamagata. The amounts of iodine excretion in Kobe and Hotaka were moderate, and less than those in Nishihara or Yamagata. The amounts of iodine intake in Kobe and Hotaka were less than those in Nishihara or Yamagata, but TGAb and/or TPOAb positivity was about the same in Nishihara, Yamagata, Kobe, and Hotaka. The differences in dietary iodine intake do not affect TGAb and/or TPOAb positivity.

Thyroid-stimulating antibody and TSH-binding inhibitor immunoglobulin in 277 Graves' patients and in 686 normal subjects.

TSH receptor antibodies (TRAb) are believed to cause hyperthyroidism of Graves' disease. Thyroid-stimulating antibody (TSAb) and TSH-binding inhibitor immunoglobulin (TBII) have been measured as TRAb to diagnose Graves' disease and to follow Graves' patients. We intended to evaluate the clinical value of TRAb (TSAb and TBII) assay in establishing the diagnosis of Graves' disease and in predicting its clinical course. TSAb and TBII were studied in 686 normal subjects and in 277 Graves' patients before antithyroid drug therapy. We followed serial changes of TSAb and TBII in 30 Graves' patients before, during and after antithyroid drug therapy over 3.5-9 yr. We measured TSAb as a stimulator assay and TBII as a receptor assay. Both TSAb and TBII were distributed normally in 686 normal subjects. ROC curves demonstrated that both TSAb and TBII had high sensitivity and specificity for the diagnosis of Graves' disease, and were equally sensitive and specific; 150% was chosen as cut-off value for TSAb and 10% for TBII. Of the 277 untreated Graves' patients, 254 (92%) had positive TSAb and positive TBII. All of the 277 untreated Graves' patients had positive TRAb (TSAb and/or TBII). We followed the serial changes of TSAb and TBII in 30 Graves' patients over 3.5-9 yr. During antithyroid drug therapy, TSAb and TBII activities decreased and disappeared in 27 patients (Group A), but continued to be high in the other 3 (Group B). The former 27 Group A patients achieved remission, but the latter 3 Group B patients continued to have hyperthyroidism. Of the 27 Group A patients, 16 (59%) had parallel decreases of TSAb and TBII activities; in 6, the changes were predominantly observed in either TSAb or TBII, and in 4, complex changes in TSAb and TBII activities were observed. Disappearance of TSAb and appearance of TSBAb was seen in one. The other 3 Group B patients continued to have high TSAb and TBII activities and to have hyperthyroidism. In conclusion, TSAb and TBII are of clinical value in establishing the diagnosis of Graves' disease and in predicting its clinical course. We clearly demonstrated its diagnostic usefulness. Both TSAb and TBII have high sensitivity and specificity. All of the 277 untreated Graves' patients had TRAb (TSAb and/or TBII). Serial changes of TSAb and TBII during therapy differ from one patient to another, and can be classified into several groups. Changes in TSAb and TBII activities reflect the clinical courses of Graves' patients. The simultaneous measurement of both TSAb and TBII is clinically useful, since TSAb and TBII reflect two different aspects of TRAb. TSAb and TBII are different.

High prevalence of GAD65 (and IA-2) antibodies in Japanese IDDM patients by a new immunoprecipitation assay based on recombinant human GAD65.

Marked differences have been reported in the prevalence of glutamic acid decarboxylase (GAD) antibodies between Caucasian (63-84%) and Japanese (30-50%) or Asian (5-50%) IDDM patients. Using a new immunoprecipitation assay based on 125I-labelled recombinant human GAD65 we have reassessed prevalence of GAD65 antibodies in Japanese patients. We also assessed prevalence of IA-2 antibodies. GAD65 antibodies were detected in 83.3% of sera taken within 1 year of onset, comparable to the prevalence reported in Caucasian patients. Positivity decreased to 66.7% after 2 to 3 years and to 54.3% after 3 years from onset, still higher than previously reported Asian prevalence. Except in one patient, high antibody levels persisted chronically, up to 12 years. There was no difference in the prevalence of GAD65 antibodies between Japanese IDDM patients with and without autoimmune thyroid disease (AITD). IA-2 antibodies were detected in 64.7% of sera taken within 1 year of onset. Prevalence of IA-2 antibodies was lower than that of GAD65 antibodies. The difference in positivity in Asian IDDM patients between present and previous reports arose from the sensitivity of our assay for GAD65 antibodies. Additionally, the patients we studied had classic IDDM with a well-defined onset. We conclude that prevalence of GAD65 antibodies in Japanese IDDM patients is comparable to that in Western studies. There was no relationship of GAD65 antibody positivity to coexistence of AITD. Our results suggest that autoimmunity is the most significant cause of Japanese IDDM.

An abnormal sodium metabolism in Japanese patients with essential hypertension, judged by serum sodium distribution, renal function and the renin-aldosterone system.

OBJECTIVE: The role of the renin-aldosterone system and the ability of renal sodium reabsorption to facilitate pressure natriuresis were analyzed by using a sufficient number of Japanese patients with essential hypertension. METHODS: We studied 3222 normal Japanese subjects (610 in Kashiwa City Hospital and 2612 in Shinshu University Hospital), 741 Japanese patients with essential hypertension (256 in Kashiwa City Hospital and 485 in Shinshu University Hospital), 20 patients with aldosterone-producing adenomas and 11 patients with idiopathic hyperaldosteronism to determine the possible roles of sodium, renal function, and plasma aldosterone concentration (PAC) on blood pressure elevation. Inappropriate elevation of aldosterone levels [elevation of the aldosterone:plasma renin activity (PRA) ratio] was used to assess aldosterone action. RESULTS: The peak of the serum sodium distribution curve was approximately 2 mmol/l higher in the patients with essential hypertension than it was in controls. The prevalence of higher serum sodium concentrations (> or = 147 mmol/l) also was increased significantly hypertensive patients. Age-related deterioration of renal function did not explain the hypertension and abnormal sodium metabolism in the hypertensive patients. In stepwise regression analysis, the serum sodium concentration was related inversely to the PRA and positively to the PAC:PRA ratio. Although there was an inverse relationship between urinary sodium excretion (representing sodium intake) and the PRA, urinary sodium excretion proved not to be significant as a source of variation in the PAC or in the PAC:PRA ratio in the hypertensive patients. Although the PAC was within the normal range in patients with serum sodium concentrations of 147 mmol/l or more and an elevated PAC:PRA ratio, it was inappropriately high for the stimulus applied, as indicated by the PRA; this is similar to the situation with aldosterone-producing adenomas or idiopathic hyperaldosteronism. CONCLUSION: Serum sodium distribution patterns differed between normal subjects and patients with essential hypertension in this Japanese population. The deterioration of renal function and increased sodium intake did not explain this abnormal sodium metabolism. A higher serum sodium concentration is related to an elevated blood pressure, and, in some patients, an inappropriate elevation of plasma aldosterone levels. Of the Japanese hypertensive patients, 10-14% exhibited serum sodium concentrations of 147 mmol/l or more and inappropriate elevations of aldosterone level (suppressed PRA and normal aldosterone level). The defect in these patients presumably lies in the inappropriately high secretion of aldosterone.

Association of HTLV-I with autoimmune thyroiditis in patients with adult T-cell leukaemia (ATL) and in HTLV-I carriers.

OBJECTIVE: Human T-lymphotrophic virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukaemia (ATL). This virus is associated with a variety of autoimmune disorders. The possible association between HTLV-I Infection and autoimmune thyroiditis has not been fully studied. We therefore evaluated anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TGAb) in the sera of patients with ATL, carriers of HTLV-I, and in healthy control subjects to investigate the possible association between such infection and auto-immune thyroiditis. PATIENTS AND METHODS: Fifty-two ATL patients (21 males, 31 females; mean age 56.4 years) and 50 HTLV-I carriers (18 males, 32 females; mean age 56.7 years) were studied. The control subjects were 877 healthy adults (271 males, 606 females; mean age 54.8 years) who were negative for HTLV-I antibody. TPOAb, TGAb, thyroxine (T4) and thyrotrophin (TSH) were measured in serum using a radioimmunoassay kit. RESULTS: Positivity for thyroid autoantibodies (TPOAb and/or TGAb) was found in 21 of 52 ATL patients (40.4%), 15 of 50 HTLV-I carriers (30.0%), and 120 of 877 control subjects (13.7%). The difference between the HTLV-I-Infected and the control subjects was statistically significant (P < 0.005). Female control subjects had a significantly higher prevalence of positivity for thyroid autoantibodies than the males (17.3 vs 5.5%, P < 0.001). Carriers of HTLV-I and patients with ATL of each sex showed an equally high prevalence of positivity for thyroid autoantibodies. Of the subjects who were positive for thyroid autoantibody, 7.5% of control subjects, 19.0% of ATL patients, and 40.0% of HTLV-I carriers had hypothyroidism. A significant difference in this respect was noted between the HTLV-I infected subjects and the control subjects (P < 0.005). CONCLUSIONS: This study demonstrates a high prevalence of positivity for thyroid autoantibodies (TPOAb and/ or TGAb) in the adult T-cell leukaemia patients and the HTLV-I carriers. The adult T-cell leukaemia patients and the HTLV-I carriers each had a high prevalence of hypothyroidism. There was an association between HTLV-I infection and autoimmune thyroiditis.

Simple and reliable method for predicting the remission of Graves' disease: revised triiodothyronine-suppression test, indexed by serum thyroxine.

To find a simple and reliable method for predicting the long-term remission of Graves' disease, we studied the outcome of 182 methimazole-treated patients with Graves' disease, whose thyroidal RAIU became < 12% after T3 administration. The patients were treated with methimazole over 2 years. T3 suppression test was done 6 months after the disappearance of TSH-receptor antibody (TRAb); the patients took T3 for 14 days, and on the 14th day, blood was obtained for serum T3, T4, and TSH determination, and RAIU was measured. These 182 patients were followed for 5 years after methimazole withdrawal. We divided the 182 methimazole-treated patients, whose thyroidal RAIU became < 12% after T3 administration, into two groups based on the outcome after the discontinuation of methimazole; 40 patients (22%) had an overt recurrence (group A) and the other 142 (78%) did not (group B). The degree of serum T4 suppressibility by T3 was less in group A than in group B. In group A, the number of the patients with a serum T4 < 60% of the pre-T3 levels is less than that with a serum T4 > or = 60%, but, in group B the former is more than the latter. The serum T4 < 60% of the pre-T3 level was significantly associated with the remission.(ABSTRACT TRUNCATED AT 250 WORDS)