Search PubMed⌕ Search

Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 397 records · Page 22Linked to original sources
PubMed1995

Hematopoietic stem cells found in lineage-positive subsets in the bone marrow of 5-fluorouracil-treated mice.

It is known that treatment of mice with 5-fluorouracil (5-FU, 150 mg/kg) confers radioprotection. To investigate this effect, we performed bone marrow transplantation (BMT) using C57BL/6-Ly5 congenic mice treated with 5-FU five days prior to experiments. The mononuclear cells (MNC) in 5-FU-treated bone marrow (BM) were 10 times more radioprotective than those in untreated BM. Moreover, the number of BM MNC expressing c-kit on their surface from 5-FU-treated mice was markedly decreased relative to those from untreated controls. These results showed that the surface characteristics of cells that contributed to this radio-protective effect differ from those of stem cells as reported recently. BM MNC of mice treated with 5-FU were separated on the basis of expression of the lineage-specific antigens (Lin), c-kit, and Ly6A/E. When injected into lethally irradiated mice, 1,000 Lin+ and Lin-c-kit+Ly6A/E+ cells showed radioprotective effects such that 100% and 60% survived, respectively. Flow cytometric analysis 165 days after BMT showed that 88.8% and 65.1% of peripheral blood (PB) in mice transplanted with Lin+ and Lin-c-kit+Ly6A/E+ was derived from donor mice, respectively. After six months, donor-derived Lin-c-kit+Ly6A/E+ cells which showed radioprotective effects on a secondary irradiated host were detected from mice transplanted with Lin+ cells from 5-FU-treated mice. Taken together, these findings demonstrated that stem cells expressing Lin+ present in the BM of mice treated with 5-FU other than Lin-c-kit+Ly6A/E+ cells and these Lin+ cells play an important role in the recovery of myeloablative mice.

Animals↗
PubMed1995

Effect of leukotriene C4D4 antagonist on colonic damage induced by intracolonic administration of trinitrobenzene sulfonic acid in rats.

We examined the effects of eicosanoid antagonists on colonic damage induced by trinitrobenzene sulfonic acid (TNB) in a rat inflammatory bowel model. TNB (30 mg) dissolved in 0.25 ml of 50% ethanol, was given intrarectally. The appropriate doses of ONO-1078 (a leukotriene C4D4 antagonist), ONO-4057 (a leukotriene B4 antagonist), and OKY-046 (a thromboxane A2 synthetase inhibitor) were given to obtain the same blood level, either 4 h before (pre-treatment model) or 24 h after (the post-treatment model) the administration of TNB (n = 8 in all groups). Drugs were given once daily for 6 days through a gastric feeding tube. Autopsy was performed on the 7th day. Colonic damage was assessed in terms of colonic damage scores, and myeloperoxidase (MPO) activity and eicosanoid concentrations in colonic tissues were measured. Compared with the group given TNB alone, the colonic damage score was reduced to 10% in the pre-treatment model with ONO-1078, but the score was not reduced in other groups, MPO activity was not changed in any group. The concentration of leukotriene C4 was reduced with ONO-1078 treatment, in both pre- and post-treatment models. These results demonstrated that a leukotriene C4D4 antagonist reduced colonic inflammation; however, its anti-inflammatory effect was limited in this colitis model.

Animals↗
PubMed1995

Association of idiopathic hypopituitarism and syringomyelia.

The magnetic resonance in an 8-year-old boy with hypopituitarism and cervical syringomyelia are presented. Magnetic resonance imaging of the brain clearly demonstrated syringomyelia in the cervical spinal cord and transection of the pituitary stalk, findings identical to those reported in the literature. Both disorders have been seen in association with a difficult labor, so we suggest that this is not a chance finding.

Child↗
PubMed1995

Design for cell-specific targeting of proteins utilizing sugar-recognition mechanism: effect of molecular weight of proteins on targeting efficiency.

Hepatic targeting of proteins utilizing the sugar-recognition mechanism was investigated in mice after intravenous injection. Five proteins with different molecular weights, i.e., bovine gamma-globulins (IgG), bovine serum albumin (BSA), recombinant human superoxide dismutase (SOD), soybean trypsin inhibitor (STI), and chicken egg white lysozyme (LZM), were modified with 2-imino-2-methoxyethyl 1-thiogalactoside to obtain galactosylated proteins (Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM). The numbers of galactose residues were 38, 20, 11, 6, and 5 for Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM, respectively. All galactosylated proteins were dose-dependently taken up by the liver and the relative amount accumulated in the liver was decreased with an increase of the administered dose. At low doses (0.05 and 0.1 mg/kg), Gal-IgG, Gal-BSA, and Gal-SOD could be taken up by the liver up to more than 70-80% of dose within 10 min after intravenous injection, but the maximum amounts accumulated in the liver were approximately 40 and 30% of the dose for Gal-STI and Gal-LZM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

A case of iatrogenic growth retardation induced by a corticosteroid-containing anti-allergic drug.

A nine-year old boy developed reduced growth velocity at the age of seven. The peak plasma growth hormone (GH) response to 3,4-dihydroxyphenylalanine, GH-releasing factor and insulin was 10.2, 8.1 and 7.6 micrograms/l, respectively, suggesting that the GH reserve was slightly reduced. Serum cortisol was undetectable and urinary excretion of 17-hydroxycorticosteroid was low (0.22-0.31 mg/day), but there were no physical or biochemical signs of adrenocortical insufficiency. He had taken an anti-allergic drug containing 0.25 mg of betamethasone and 2 mg of d-chlorpheniramine maleate per tablet for about 2 years to treat allergic rhinitis. Catch-up growth occurred when this drug was stopped. The present case suggests that daily administration of 0.25 mg of betamethasone can induce growth retardation and that ingestion of corticosteroid-containing preparations needs to be excluded in children who develop short stature without other symptoms.

17-Hydroxycorticosteroids↗
PubMed1995

Effects of monoclonal antibody against CD45RB on peripheral blood mononuclear cell proliferation and on HLA-DR and adhesion molecule expression on thyrocytes of patients with autoimmune thyroid disease.

To evaluate the role of CD45 (especially that of the ectodomain region B) on immunocyte-thyrocyte signaling in patients with autoimmune thyroid disease (AITD), we have examined the in vitro and in vivo effects of a monoclonal antibody (mAb) against with CD45RB, termed MT3. MT3 was added to cultured peripheral blood mononuclear cells (PBMC) from patients with AITD and was additionally injected into severe combined immunodeficient (SCID) mice to which Graves' thyroid cells and intrathyroidal lymphocytes were engrafted. MT3 stimulated proliferation of PBMC when cultured for 2 to 3 days in patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) and in normal controls (NC). However, when cultured for 7 days, the stimulation index [SI: counts per minute (cpm) with mAb/cpm without mAb] was lowered by MT3 in NC and GD patients. However, the mean SI was not lowered in patients with HT. In SCID mice, the concentrations of human immunoglobulin G, antithyroglobulin and antithyroperoxidase antibodies in sera were not significantly changed by injecting MT3. The expression of human leukocyte antigen (HLA)-DR and intercellular adhesion molecule (ICAM)-1 on engrafted human thyrocytes decreased after the tissues were engrafted into the control mice to which vehicle alone was injected. However, in the mice injected with MT3, HLA-DR and ICAM-1 expression remained high or up-regulated by the injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Homing of 51Cr-labeled human peripheral lymphocytes to Graves' thyroid tissue xenografted into SCID mice.

We have recently described a NUDE/SCID mouse model that has been useful for the study of human thyroid autoimmunity in in vivo conditions. The reappearance of lymphocytic infiltration in Graves' thyroid tissue and a humoral response in SCID mice (rexenografted with normalized thyroid tissues from NUDE mice) was detected only if autologous Graves' human peripheral lymphocytes (PBMC) were engrafted into the same animals. Therefore it was presumed that some autoreactive PBMC directed themselves to the thyroid. However, there was previously no direct evidence regarding the trafficking of the engrafted PBMC to the target tissue. To elucidate this point we have studied the migration of 51Cr-labeled PBMC in SCID mice. Human thyroid tissue from six Graves' disease (GD) patients and six patients with nontoxic nodular goiter were initially xenografted into NUDE mice for 8 weeks. The same tissues were retrieved and rexenografted into several "virgin" SCID mice, i.e., no previous xenografts. Autologous PBMC were isolated from blood of the same patients obtained at the time of the tissue rexenograftment and labeled with radioactive 51Cr. Twenty million labeled PBMC were engrafted into each SCID mouse. The distribution of labeled lymphocytes into mouse organs and trafficking into Graves' and normal xenografts was measured. A significant amount of radioactivity in Graves' xenografts was detected after 1 week with the peak of radioactivity at 2-3 weeks. This radioactivity was significantly higher than radioactivity in surrounding tissues (skin, muscle). In contrast, homing of autologous lymphocytes into normal paranodular thyroid tissue was very minimal; the radioactivity of GD thyroid xenografts with engrafted autologous lymphocytes was significantly higher than that of normal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Purification and properties of L-galactono-gamma-lactone dehydrogenase, a key enzyme for ascorbic acid biosynthesis, from sweet potato roots.

L-Galactono-gamma-lactone dehydrogenase (L-galactono-gamma-lactone:ferricytochrome c oxidoreductase [EC 1.3.2.3], GLDHase) which catalyzes the terminal step in the biosynthesis of L-ascorbic acid (AsA) has been purified from roots of sweet potato (Ipomoea batatas L., cv. Kintoki). Highly purified preparation of the GLDHase was obtained by three column chromatography steps with a recovery of ca. 1%, after solubilization from mitochondria in sweet potato roots. SDS-PAGE exhibited a single band at 56 kDa. In the native state, the apparent molecular mass of the enzyme was 56 kDa, based on a Sephadex G-100 gel filtration. The pI and optimum pH values were 5.8 and 7.9, respectively. The Km value for L-galactono-gamma-lactone was 0.12 mM. Substrate inhibition was obtained at concentrations greater than 4.2 mM. The enzyme was inhibited by p-chloromercuribenzoate (PCMB) and acriflavine, and the inhibition of acriflavine was diminished by the addition of FAD or FMN. The only effective substrate for the GLDHase was L-galactono-gamma-lactone.

Ascorbic Acid↗
PubMed1995

Carbachol and cholecystokinin enhance accumulation of nicotine in rat pancreatic acinar cells.

Nicotine is a possible risk factor for chronic pancreatitis and pancreatic cancer. To study the loci where nicotine might exert its effect, we examined interactions between nicotine and rat pancreatic acini. When pancreatic acini were incubated with [3H]nicotine, [3H]nicotine levels in pancreatic acini were increased in time-and dose-dependent manners, and the t1/2 for dissociation of [3H]nicotine was 63.8 min. At 4 degrees C, the association of [3H]nicotine was 33% of the association at 37 degrees C. Unlabeled nicotine had no significant effect on the accumulation of [3H]nicotine. In addition, surface-bound [3H]nicotine was not detected when acini were washed in a low-pH solution or when they were trypsinized. These results suggest that the accumulation of nicotine may be a biological phenomenon and that [3H]nicotine does not bind to surface receptors of acinar cells, but accumulates intracellularly. The addition of verapamil (0.1 mM) or 12-O-tetradecanoylphorbol-13-acetate (1 microM) had no effect on [3H]nicotine association, while 4-bromo-A23187 (2 microM) or EGTA (10 mM) significantly increased the accumulation of [3H]nicotine. Carbachol and cholecystokinin significantly enhanced the accumulation of [3H]nicotine in a dose-dependent manner. Taken together, the increasing effects of carbachol and cholecystokinin on the accumulation of nicotine may explain, at least in part, the mechanisms involved in the multiplicative effects of the combination of two risk factors, smoking habit and high-fat or high-protein diets, on human pancreatic diseases.

Animals↗
PubMed1995

Effects of diet on cholecystokinin-stimulated amylase secretion by pancreatic Acini and amylase mRNA levels in rat pancreas.

To investigate the mechanisms by which dietary compositions regulate the exocrine pancreas, we examined the effects of no-fat diet (NFD) and high-fat diet (HFD) on cholecystokinin (CCK)-stimulated amylase secretion from rat pancreatic acini. Rats were maintained for 4 weeks on NFD or HFD, which contained 0 or 45% fat and 58 or 29% carbohydrates, respectively. Pancreatic acini were isolated and stimulated by graded doses of CCK for 30 min. Maximal CCK-stimulated amylase secretion by pancreatic acini from rats on NFD (23.1 +/- 4.3 U/mg protein at 10(-10) M) was significantly higher than that of HFD (5.5 +/- 1.6 U/mg protein at 10(-10) M). In contrast, expressed as a percentage of the initial content, maximal CCK-stimulated amylase secretion by pancreatic acini from rats on NFD (15.0 +/- 0.8%) tended to be lower than that from rats on HFD (28.1 +/- 3.5%). To study further the effects of the diets on amylase mRNA levels, another group of rats was maintained on the respective diets for 4 weeks, sacrificed, and total pancreatic RNA isolated. Amylase mRNA levels in rats on NFD were 2.5 times higher than in rats on HFD. The results suggest that alterations in CCK-stimulated amylase secretion by pancreatic acini, as well as modifications in pancreatic amylase expression, may be involved in the mechanisms by which the exocrine pancreas adapts to diet.

Amylases↗
PubMed1995

Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties.

The recognition of 111In-labeled galactosylated superoxide dismutase (Gal-SOD) and galactosylated bovine serum albumin (Gal-BSA) by the liver was investigated in mice after intravenous injection. 111In-labeled galactosylated proteins were recovered in the liver by amounts that were highly dependent on the degree of galactose modification and the administered dose. The distribution patterns were analyzed based on a physiological pharmacokinetic model including an uptake process with Michaelis-Menten kinetics in the liver and hepatic plasma flow. The Michaelis constant of hepatic uptake of 111In-Gal-SOD was observed to inversely correlate with the number of galactose residues, without a significant change in maximum rate of uptake or extrahepatic clearance. This relation could be applied to 111In-Gal-BSA and other galactosylated proteins by using the surface density of galactose residues as a degree of modification, suggesting galactose density controls ligand recognition by the asialoglycoprotein receptor. The analysis also indicated that increasing galactose density higher than 1.0 x 10(-3) molecules/A2 did not affect the distribution of galactosylated proteins due to limitation by the hepatic plasma flow rate. In conclusion, efficient delivery of proteins modified with galactose to the liver will be achieved by controlling both the galactose density on the protein surface and the administered dose.

Animals↗
PubMed1995

Glucocorticosteroids increase beta 2-adrenergic receptor transcription in human lung.

beta 2-Adrenergic receptors (beta 2R) are widely distributed and mediate a wide range of cellular responses in lung. Because glucocorticosteroids increase expression of beta 2R in cell lines, we have investigated the effects of glucocorticoids on the beta 2R mRNA level and the number of beta 2R in human peripheral lung in vitro. Incubation of lung tissues with dexamethasone (Dex) elevated both beta 2R mRNA level (as measured by Northern blot analysis) and beta 2R number (as measured by [125I]iodocyanopindolol binding). The increased accumulation of beta 2R mRNA could be detected at 15 min (1.27 +/- 0.1-fold) and the maximal accumulation occurred at 2 h (2.73 +/- 0.5-fold). The Dex-induced increase in beta 2R mRNA returned to the control level by 17 h. The increase in beta 2R number (1.58 +/- 0.2-fold) was slower, reaching a maximum between 17 and 24 h. Dex increased beta 2R mRNA in a time- and concentration-dependent manner that was abolished by the steroid receptor antagonist mifepristone (RU-38486 or RU-486). The stability of beta 2R mRNA was unchanged by Dex, and a nuclear run-on assay revealed that Dex approximately doubled the transcriptional rate of the beta 2R gene. These observations suggest that glucocorticoids act on steroid receptors to increase beta 2R expression by increasing the rate of beta 2R gene transcription.

Adolescent↗
PubMed1995

Protective effects of a glucocorticoid on downregulation of pulmonary beta 2-adrenergic receptors in vivo.

We investigated the in vivo effects of a glucocorticoid on beta-agonist-induced downregulation of beta 1- and beta 2-adrenergic receptors (determined by [125I]iodocyanopindolol binding), mRNA expression (assessed by Northern blotting), and gene transcription (using nuclear run-on assays) in rat lung. Dexamethasone (Dex) (0.2 mg/kg/d, days 1-8) increased beta 1- and beta 2-receptor numbers by 70 and 69% above control, respectively, but did not change their mRNA expression. Isoproterenol (Iso) (0.96 mg/kg/d, days 2-8) decreased beta 1- and beta 2-receptor numbers by 48 and 51%, respectively, and also reduced mRNA expression by 69 and 57%, respectively. The combination of Dex and Iso resulted in no net change in beta 2-receptor number and its mRNA expression, although there was a significant reduction in beta 1-receptor number and mRNA expression. The mapping of beta 1- and beta 2-receptors by receptor autoradiography confirmed these findings over alveoli, epithelium, endothelium, and airway and vascular smooth muscle. We also measured the activation of the transcription factor, cyclic AMP response element binding protein (CREB) using an electrophoretic mobility shift assay. CREB-like DNA-binding activity was decreased after Iso treatment but this decrease was prevented after treatment with Dex. Nuclear run-on assays revealed that the transcription rate of the beta 1-receptor gene did not alter after Dex treatment, but was reduced after Iso treatment. The transcription rate of the beta 2-receptor gene was increased after Dex treatment by approximately twofold, but there was no change after Iso treatment. We conclude that glucocorticoids can prevent homologous downregulation of beta 2-receptor number and mRNA expression at the transcriptional level without affecting beta 1-receptors and that the transcription factor CREB may be involved in this phenomenon. Such an effect may have clinical implications for preventing the development of tolerance to beta 2-agonists in asthmatic patients treated with beta-agonist bronchodilators.

Animals↗
PubMed1995

Expression of intercellular adhesion molecule-1 on human thyroid cells from patients with autoimmune thyroid disease: study of thyroid xenografts in nude and severe combined immunodeficient mice and treatment with FK-506.

It has been suggested that intercellular adhesion molecule-1 (ICAM-1) may play an important role in the initiation, localization, and perpetuation of autoimmune thyroid diseases (AITD). In an effort to clarify its role, we have investigated the expression of ICAM-1 on thyroid epithelial cells (TEC) of patients with AITD, patients with nontoxic goiter (NTG), and normal subjects (PN) by flow cytometric analysis under basal conditions and after modulation with cytokines, before and after 8 weeks of thyroid tissue xenotransplantation in nude athymic mice (which lyses all passenger lymphocytes), and in severe combined immunodeficient (SCID) mice where these cells survive. Before xenografting, ICAM-1 was expressed on 56% of TEC from Hashimoto's thyroiditis (n = 5), 54% of Graves' disease (n = 6), 15% of NTG (n = 5), and 12% of PN TEC. After the xenografts had been 8 weeks in nude mice, ICAM-1 expression decreased markedly in AITD TEC [from 56% to 10% in Hashimoto's thyroiditis (P < 0.001) and from 54% to 8% in Graves' disease (P < 0.01)], but did not change significantly in NTG or PN. After the xenografts had been 8 weeks in SCID mice, the expression of ICAM-1 was significantly higher on TEC of AITD compared with the same tissue in nude mice. When the SCID mice engrafted with AITD tissue were treated with the anti-CD4+ T (helper) cell agent FK-506, the expression of ICAM-1 was reduced significantly compared with that in the original tissue or that in nontreated mice engrafted with the same tissue. The proportion of TEC that were ICAM-1 positive was up-regulated in all cases by certain cytokines (e.g. interferon-gamma and tumor necrosis factor-alpha applied alone or in combination). We also detected the presence of ICAM-1 in AITD frozen tissues using an immunohistochemical technique. These data suggest a role for ICAM-1 in human AITD. However, the expression of ICAM-1 appears to be a secondary phenomenon in response to the immune assault, rather than a primary event. Our results support the idea that TEC may act as passive captives to immunological events in human AITD.

Animals↗
PubMed1995

Bioactivity of thyrotropin (TSH) in patients with central hypothyroidism: comparison between in vivo 3,5,3'-triiodothyronine response to TSH and in vitro bioactivity of TSH.

To investigate the cause(s) of central hypothyroidism with normal or elevated TSH concentrations, we evaluated the bioactivity of serum TSH as well as pituitary and thyroid function. Seven hypothyroid patients had documented deficiencies of anterior pituitary hormones other than TSH. Basal TSH concentrations ranged from 2.2-14.8 microU/mL. Six patients had low T4 and free T4 concentrations; the remaining patient had a low free T4 and a low normal T4 level with an elevated TSH concentration of 14.4 microU/mL. The mean increment in TSH 30, 60, and 90 min after TRH administration (mean delta TSH) in these patients was 13.5 +/- 9.1 microU/mL (mean +/- SD), which was not significantly different from the value in controls (9.2 +/- 3.5 microU/mL). However, the ratio of the T3 increment at 120 min (delta T3) to mean delta TSH (delta T3/mean delta TSH) in patients was 53.9 +/- 29.3 ng/microU, significantly lower than the control value of 239.5 +/- 97.5 ng/microU (P < 0.01), suggesting that the thyroid response to endogenous TSH was blunted. The serum T4 concentration correlated with the mean delta TSH in these patients (r = 0.78; P < 0.05), suggesting that hypothyroidism is dependent on conserved pituitary function. The mean bioactivity to immunoreactivity ratio of basal TSH in patients was 0.97 +/- 0.27 and was not significantly different from the normal value of 1.05 +/- 0.22. One of the two patients with high basal TSH (> 10 microU/mL) had a ratio of 0.59, which is just below the mean +/- SD of normal subjects (0.61), suggesting that most patients had normal TSH bioactivity in vitro. Our findings suggest that in vivo bioactivity of TSH is decreased because of a pituitary disorder, but in vitro bioactivity of TSH is variable in patients with central hypothyroidism.

Adult↗
PubMed1995

[Effect of the novel calcium antagonist AE0047 on responses of isolated dog blood vessels to vasoconstricting agents and to nerve stimulation].

The effect of AE0047 on contractile responses to high K+ and agonists and to perivascular nerve stimulation was investigated using isolated dog cerebral, coronary and mesenteric arteries and mesenteric veins. AE0047 inhibited concentration-dependent contractions induced by KCl, norepinephrine, prostaglandin (PG) F2 alpha and serotonin. The inhibition of contractions caused by PGF2 alpha and serotonin was greater in cerebral arteries than in mesenteric arteries. The inhibitory effect of AE0047 on norepinephrine-induced mesenteric arterial contraction persisted for 24 hr or longer even though the strips were repeatedly washed. Greater inhibition was obtained in the arteries contracted with K+ than in those contracted with agonists. AE0047 reduced Ca(2+)-induced contraction in K(+)-depolarized mesenteric artery strips to a greater extent than those in PGF2 alpha-stimulated strips. The relaxation induced by transmural electrical stimulation in coronary arteries treated with phenotolamine was reduced by AE0047, whereas the norepinephrine-induced relaxation was unaffected. In cerebral arteries treated with superoxide dismutase, AE0047 reduced nicotine-induced relaxation but not NO-induced relaxation. These findings suggest that AE0047 selectively inhibits vasocontractions via voltage-dependent Ca channels and preferentially inhibits cerebroarterial contraction, these actions being long-lasting. AE0047 appears to reduce the release of neurotransmitter from adrenergic and nitroxidergic nerve terminals in blood vessels.

Animals↗
PubMed1995

Thyroid stimulating antibody in sera of Graves' ophthalmopathy patients as a possible marker for predicting the efficacy of methylprednisolone pulse therapy.

Nine patients with Graves' ophthalmopathy (GO) were treated with intravenous methylprednisolone pulse therapy and followed up by ophthalmological assessment, magnetic resonance imaging, and thyroid-associated autoantibody (thyroid stimulating antibody (TSAb), TSH binding inhibitor immunoglobulins (TBII), and anti-eye muscle antibody (EMAb)). Ophthalmological assessment was performed by the ophthalmopathy index (OI) which was made on the basis of the system recommended by the American Thyroid Association Committee. EMAb was expressed as the ratio of density of the 64 kDa band of eye muscle membrane to that of 92 kDa non-specific band found with all normal sera when assessed by western blotting. Five patients with mild ophthalmopathy (OI < 4) did not show progressive improvement in OI. Three of 4 patients with severe eye disease (OI > 4) showed a progressive and distinct improvement in OI. These 3 patients had high TSAb levels before methylprednisolone pulse therapy. One patient with severe ophthalmopathy did not respond to this pulse therapy; this patient's TSAb was negative. A significant positive correlation was observed between the activity of TSAb before treatment and the improvement in OI (delta OI) (r = 0.86, P < 0.01, n = 9). The relationship between delta OI and EMAb did not reach significance. These results suggest that TSAb in sera of GO patients can be a useful marker for predicting the efficacy of methylprednisolone pulse therapy.

Adolescent↗