Biomedical subjects

Y Hiromatsu

Publications and source records attributed to Y Hiromatsu.

At least 37 records · Page 2Linked to original sources

PubMed1998

Nicotinamide decreases cytokine-induced activation of orbital fibroblasts from patients with thyroid-associated ophthalmopathy.

We used flow cytometry to investigate the effects of nicotinamide, an inhibitor of poly (ADP ribose) synthetase, on the cell-surface expression of cytokine-induced human leukocyte antigen (HLA)-A,B,C antigen, HLA-DR antigen, intercellular adhesion molecule 1, CD44, and Fas expression in cultured orbital fibroblasts from patients with thyroid-associated ophthalmopathy. After two to seven passages, cultured orbital fibroblasts were incubated for 3 days with interferon gamma or tumor necrosis factor alpha in the presence of nicotinamide. Nicotinamide inhibited the induction of both HLA-DR and intercellular adhesion molecule 1 expression by cytokines on fibroblasts but did not interfere with induction of HLA-A,B,C, or CD44 expression. Nicotinamide also inhibited the proliferation of orbital fibroblasts, as assessed by a [3H]-thymidine incorporation assay and cell counts. Nicotinamide also enhanced the expression of the apoptosis-mediating protein Fas on fibroblasts. Our data suggest that nicotinamide inhibits cytokine-induced activation of fibroblasts and thus may decrease the autoimmune injury to the orbit in thyroid-associated ophthalmopathy.

Adipose Tissue↗

PubMed1998

The 64-kilodalton eye muscle protein is the flavoprotein subunit of mitochondrial succinate dehydrogenase: the corresponding serum antibodies are good markers of an immune-mediated damage to the eye muscle in patients with Graves' hyperthyroidism.

Thyroid-associated ophthalmopathy (TAO) is a progressive eye disorder associated with thyroid autoimmunity, particularly Graves' hyperthyroidism, which is generally considered to have an autoimmune etiology. Eye muscle membrane proteins reportedly of 55 and 64 kDa are the best markers of the ophthalmopathy. The main focus of our recent studies has been to purify the pertinent proteins from porcine eye muscle membranes and characterize them. The 64-kDa protein is now shown from a partial sequence and by Western blotting using specific antibody probes to be the flavoprotein (Fp) subunit of succinate dehydrogenase and to have a correct molecular mass of 67 kDa. The protein was purified and cleaved with cyanogen bromide, and the N-terminal region of an immunoreactive partial peptide was determined. The 20-amino acid porcine sequence so obtained matched one within the Fp subunits of human and bovine succinate dehydrogenases in 20 and 18 of these positions, respectively. Succinate dehydrogenase is both a citric acid cycle enzyme and a component (complex II) of the mitochondrial respiratory chain. It is thus essential for aerobic energy production and is highly conserved. The mature human and bovine Fp subunits are 92% homologous and have a molecular mass of approximately 67 kDa, the same as our redetermined value for the 64-kDa marker protein. Sera from patients with TAO and from those with Graves' hyperthyroidism without evident ophthalmopathy highlighted the 64-kDa marker protein in crude porcine eye muscle membranes and the Fp subunit of highly purified bovine succinate dehydrogenase at the identical position on Western blots. Anti-beef Fp antibodies were detected in sera from 67% of patients with active TAO of more than 1-yr duration, in 30% with stable TAO of more than 3-yr duration, and in 30% of patients with Graves' hyperthyroidism without ophthalmopathy, but in only 7% of age- and sex-matched normal subjects. As succinate dehydrogenase is bound to the matrix (inside) surface of the mitochondrial inner membrane, it is unlikely to be accessible to circulating autoantibodies. We would postulate that eye muscle damage in ophthalmopathy is probably caused by cytotoxic antibodies or CD+ T lymphocytes targeting a cell membrane antigen, such as the thyroid and eye muscle shared protein G2s, and that presentation of succinate dehydrogenase is secondary. On the other hand, an autoantibody response to succinate dehydrogenase may be a good marker of immune-mediated damage to the eye muscle fiber and may support the idea that the extraocular muscles are targets of the autoimmune reactions of TAO.

Adult↗

PubMed1998

Comparison of technetium-99m-MIBI, technetium-99m-tetrofosmin, ultrasound and MRI for localization of abnormal parathyroid glands.

UNLABELLED: Abnormal parathyroid tissue can be identified by radionuclide imaging with either 99mTc-MIBI or 99mTc-tetrofosmin. This study compared the relative sensitivity of these two agents to localize parathyroid hyperplasia and adenoma. METHODS: Twenty patients with primary (n = 9) or secondary (n = 11) hyperparathyroidism were studied with 99mTc-MIBI and 99mTc-tetrofosmin parathyroid imaging, ultrasonography and MRI. Radionuclide images of the neck were acquired 10 min and 2-3 hr after radiopharmaceutical injection. The images were visually evaluated for abnormal focal areas of increased tracer localization in the neck and mediastinum. A parathyroid gland/normal thyroid tissue activity ratio (referred to as the P/T uptake ratio) was calculated for each positive scan. RESULTS: Of the 46 parathyroid glands surgically explored, the overall sensitivity and specificity of MIBI imaging were 83% and 83% (38/46); tetrofosmin imaging 87% and 83% (40/46); ultrasonography 78% and 40% (36/46); and MRI 80% and 60% (37/46), respectively. Both radiopharmaceuticals performed well in the nine patients found to have adenoma. The sensitivity and specificity of MIBI imaging were 100% and 100% (9/9); tetrofosmin imaging 100% and 100% (9/9); ultrasonography 78% and 67% (7/9); and MRI 100% and 100% (9/9), respectively. In the 37 glands with hyperplasia, MIBI imaging had a sensitivity of 78% and specificity of 75%; tetrofosmin imaging 84% and 75%; ultrasonography 78% and 43%; and MRI 73% and 60%, respectively. CONCLUSION: All imaging techniques localized abnormal parathyroid glands. The radiotracers have equal sensitivity for the localization of abnormal parathyroid glands. The sensitivity of these tracers was high as compared to ultrasonography or MRI.

Adenoma↗

PubMed1997

Localization of ectopic parathyroid glands using technetium-99m sestamibi imaging: comparison with magnetic resonance and computed tomographic imaging.

The aim of the study was to compare the accuracy of technetium-99m sestamibi imaging for localization of ectopic parathyroid glands in patients with hyperparathyroidism with that of magnetic resonance (MR) and computed tomographic (CT) imaging. Eleven patients with primary (n=3) or secondary (n=8) hyperparathyroidism were studied with 99mTc sestamibi parathyroid imaging CT and MR imaging. Images of the neck were acquired at 10 min and 2-3 after tracer injection. The three patients with primary hyperparathyroidism and five patients with secondary hyperparathyroidism underwent parathyroidectomy. The ectopic glands were confirmed by histopathological examination of the resected specimens. In respect of 20 parathyroid glands in the eight patients explored surgically, the sensitivity and specificity of sestamibi imaging were 70% (14/20) and 88%, respectively, those of CT, 40% (8/20) and 88%, and those of MR imaging, 60% (12/20) and 88%. Of these patients, three had parathyroid adenomas while five had hyperplasia (17 glands). Sestamibi imaging localized eight ectopic parathyroid glands, which were surgically confirmed (six were located in the thymus and two in the mediastinum). In one patient explored surgically, the ectopic gland was located outside the field of the MR coil. Although the remaining three cases of secondary hyperparathyroidism were not confirmed surgically, these patients demonstrated sestamibi uptake in five parathyroid glands, including three ectopic glands. MR images demonstrated abnormal parathyroid glands in the same regions as sestamibi imaging. Our data indicate that 99mTc-sestamibi imaging should be used initially to localize the ectopic parathyroid glands in patients with hyperparathyroidism for anatomical guidance prior to MR or CT imaging.

Choristoma↗

PubMed1997

Mutation of RET proto-oncogene in Japanese patients with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma.

To determine whether patients with medullary thyroid carcinoma (MTC) develop other endocrine neoplasms or their relatives develop MTC, we investigated the mutations in the RET proto-oncogene in patients with multiple endocrine neoplasia type 2B (MEN 2B, N = 1) and sporadic MTC (N = 6). DNA from MTC tissue and the peripheral blood was screened by polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis of exons 10 and 11. PCR products of exons 13 and 16 were also analyzed by AluI and FokI restriction enzyme digestion methods, respectively, and then sequenced. We did not find structural abnormalities in exon 10 or 11, or at codon 768 in exon 13, but a mutation at codon 918, ATG to ACG, was found in the peripheral blood and the MTC tissue from a patient with MEN 2B. The same mutation was also found in tumor tissue from 2 of 6 patients with sporadic MTC, but not in their peripheral blood.

Adult↗

PubMed1997

Mutations in exon 7 of the GTP-binding protein Gs alpha were not a common cause of pseudohypoparathyroidism with Albright's hereditary osteodystrophy in Japanese.

The identification of unique point mutations in patients with pseudohypoparathyroidism (PHP) with Albright's hereditary osteodystrophy (AHO) in different ethnic backgrounds has proved that defects within the Gs alpha gene account for Gs alpha deficiency in those patients. To search a mutation hot spot of the Gs alpha gene in Japanese patients, we have screened exons 2-13 of the Gs alpha gene for mutations in three unrelated Japanese PHP patients with AHO. We could find no abnormalities by denaturing gradient gel electrophoresis and no mutations of sequencing of exon 7 in these subjects. This suggests that mutations in exon 7 of the Gs alpha gene may not be a common cause of PHP with AHO in Japanese.

Adult↗

PubMed1997

Localization of parathyroid glands using technetium-99m-tetrofosmin imaging.

UNLABELLED: Preoperative localization of hyperactive parathyroid glands is useful to minimize operative time and reduce patient morbidity. This investigation compared the sensitivity of radionuclide imaging with 99mTc tetrofosmin with that of ultrasonography and magnetic resonance (MR) imaging in patients with hyperparathyroidism. METHODS: Twenty-six patients with primary (n = 7) or secondary (n = 19) hyperparathyroidism were imaged with 99mTc tetrofosmin, ultrasound and MR imaging of the neck and thorax to localize the lesions. The presence of hyperparathyroidism was identified by an intact parathyroid hormone in vitro assay. The parathyroid/normal thyroid tissue activity ratio was calculated for all patients with evidence of an abnormality on tetrofosmin images. Pathological findings were compared with the results of imaging in 18 of the 26 patients who underwent parathyroidectomy. RESULTS: Technetium-99m tetrofosmin scans demonstrated focal uptake in 46 glands of 26 patients. The uptake was categorized as slight in 78.3% (36/46) and intense (parathyroid/normal thyroid tissue activity ratio, > 1.4) in 21.7% (10/46). Ultrasonography and MR imaging identified 44 and 47 glands, respectively, in these patients. Eleven of the 18 patients who underwent parathyroidectomy within 1 mo after tetrofosmin imaging had hyperplastic glands, while 7 had parathyroid adenomas. Tetrofosmin imaging successfully localized 7 of 7 (100%) adenomas and 27 of 37 (73.0%) hyperplastic glands. The sensitivities of each technique for localizing abnormal parathyroid glands were 77.3% (34/44) for tetrofosmin imaging: 68.2% (20/44) for ultrasonography: and 68.2% (30/44) for MR imaging. Technetium-99m tetrofosmin uptake ratio in the 18 patients with surgical exploration was not proportional to several oxyphil cells. CONCLUSION: Technetium-99m tetrofosmin parathyroid imaging may be useful for localizing abnormal glands in patients with primary and secondary hyperparathyroidism. The sensitivity of 99mTc tetrofosmin parathyroid imaging was high as compared to ultrasonography or MR imaging. The prolonged retention of tetrofosmin may not depend on the number of mitochondria-rich oxyphil cells.

Adenoma↗

PubMed1996

Localization and clinical significance of thyrotropin receptor mRNA expression in orbital fat and eye muscle tissues from patients with thyroid-associated ophthalmopathy.

We have studied the cellular localization of thyrotropin receptor (TSH-R) mRNA in orbital fat and extraocular muscle tissues from patients with thyroid-associated ophthalmopathy (TAO) using Northern blot, reverse transcriptase polymerase chain reaction (RT-PCR), and in situ hybridization, and we correlated the findings with clinical estimates of ophthalmopathy. Although we failed to detect TSH-R mRNA in orbital tissues by Northern blot, TSH-R cDNA was amplified in orbital fat tissue from 13 of 25 patients with TAO and from 2 of 4 control subjects, in eye muscle tissue from 2 out of 7 patients with TAO, and in cultured orbital fibroblasts and subcutaneous fibroblasts from TAO patients. In situ hybridization showed that TSH-R mRNA was detected in cultured orbital fibroblasts as well as skin fibroblasts obtained from the patient. Furthermore, the expression of TSH-R mRNA in orbital fat tissue from patients with TAO significantly correlated with the orbital fat volume and the severity of ophthalmopathy, especially the extent of eye muscle dysfunction. These results suggest that the expression of TSH-R in the orbit, especially fibroblasts, may play a role in the pathogenesis and clinical manifestations of the ophthalmopathy in patients with TAO, although a secondary effect, involving fibroblasts in TAO is also possible.

Adipose Tissue↗

PubMed1995

Human histocompatibility leukocyte antigen-DR and heat shock protein-70 expression in eye muscle tissue in thyroid-associated ophthalmopathy.

To investigate the expression and localization of human leukocyte antigen (HLA)-DR and heat shock protein-70 (HSP-70) in orbital tissue from patients with thyroid-associated ophthalmopathy (TAO), we carried out an immunohistochemical study using anti-HLA-DR and anti-HSP-70 monoclonal antibodies and a streptavidin-biotinperoxidase detection system. Eye muscle tissues were obtained at surgery from 38 patients with TAO and 8 control subjects. HLA-DR expression on eye muscle cells was demonstrated in orbital tissue from 2 of 3 untreated patients and 2 of 35 patients who had been treated with orbital irradiation or corticosteroids, in all of whom lymphocytic infiltration was also demonstrated. HLA-DR was not detected on eye muscle cells from 8 normal controls studied. HLA-DR was expressed on endothelial cells and interstitial cells from almost all patients with TAO and all 8 control subjects. HSP-70 was detected in eye muscle cells from 31 of the patients with TAO, including all 3 untreated patients, and 3 of the controls. Although the degree of HSP-70 expression did not correlate with the severity of the ophthalmopathy, significant expression of HSP-70 in eye muscle cells was more often demonstrated in patients with eye disease of short duration (83%) than in those with disease of longer duration (33%). These results support the notion that eye muscle fiber is an important target of the orbital autoimmune reactions that characterize TAO.

Adult↗

PubMed1994

Localization of heat shock protein in orbital tissue from patients with Graves' ophthalmopathy using in situ hybridization.

We studied the cellular localization of heat shock protein 70 (HSP70) synthesis in human orbital tissue from patients with Graves' ophthalmopathy(GO) before and after immunosuppressive therapy. Synthesis was detected using in situ hybridization techniques. In a specimen from a GO patient in active phase, strong expression of HSP70 mRNA was detected in infiltrating lymphocytes as well as in fibroblasts. HSP70 mRNA was also detected in orbital tissue fibroblasts from GO patients following treatment, but not in control specimens. HSP70 expression in the orbital tissue of GO patients may be important in mediation of the immune process.

Adult↗

PubMed1994

Inhibitory effect of FK506 on intercellular adhesion molecule-1 (ICAM-1) expression on cultured thyroid cells.

The effect of FK506, an immunosuppressive agent, on phytohemagglutinin (PHA) or interferon gamma (IFN gamma)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured human thyroid cells from patients with Graves' disease was investigated. Primary cultured thyroid cells were incubated for three days with IFN gamma (10 to 800 U/ml) or PHA (1 to 50 micrograms/ml) in the presence of FK506. The surface expression of ICAM-1 was measured by flow cytometry. In some experiments, polyclonal anti-IFN gamma antibody was added to the culture to determine whether ICAM-1 expression was blocked. FK506 inhibited the PHA-induced ICAM-1 expression in thyroid cells, but not the induction by IFN gamma. PHA-induced ICAM-1 expression was not inhibited by the polyclonal anti-IFN gamma antibody. FK506 did not affect the proliferation of thyroid cells. This data indicates that the inhibitory effect of FK506 on ICAM-1 expression in primary cultured thyroid cells may be due to actions on infiltrating lymphocytes in the thyroid gland. Further studies are necessary to elucidate whether the inhibition of ICAM-1 by FK506 results in the suppression of autoimmune reactions in the thyroid gland.

Cells, Cultured↗

PubMed1993

Expression of the Hermes-1 (CD44) and ICAM-1 (CD54) molecule on the surface of thyroid cells from patients with Graves' disease.

From studies of binding of 51Cr-labeled T cells to human thyroid monolayers, we have postulated the existence of tissue "homing-like" receptors on thyroid cells in patients with Graves' disease (GD). In this study we have investigated whether the CD44 (Hermes-1) protein, well known as a putative human lymphocyte homing receptor, is expressed on thyroid cells in patients with GD, and if so whether its expression is influenced by interferon-gamma (IFN-gamma). Cell surface CD44, as well as CD54 (ICAM-1), another putative homing receptor, antigens were analyzed by flow cytometry and immunohistochemistry. CD44 and CD54 were both expressed on thyroid cells from untreated patients with GD, which, in the case of CD44, appeared as two peaks. IFN-gamma treatment enhanced the expression of the CD54 protein on Graves' thyroid cells and inhibited the expression of the larger of the two CD44 peaks, but not the other. Only small amounts of CD44 and CD54 were detected on normal thyroid cells, neither of which was affected by IFN-gamma. The CD44 protein was also demonstrated on both GD and normal thyroid cells by immunohistochemistry. These findings suggest that CD44, and possibly CD54, may induce putative adhesion pathways that lead to the homing of lymphocytes to the thyroid in patients who develop Hashimoto's thyroiditis and Graves' disease.

Adult↗

PubMed1993

Intravenous methylprednisolone pulse therapy for Graves' ophthalmopathy.

To investigate the efficacy of intravenous methylprednisolone pulse therapy on Graves' ophthalmopathy (GO), fifteen patients with severe GO were treated with large dose intravenous methylprednisolone (at a daily dosage of 1 g for 3 successive days). This treatment was repeated 3-5 times for 3-5 weeks. They were monitored before, 2 weeks after and 6 months after therapy by ophthalmological assessment, orbital magnetic resonance imaging (MRI), and by measuring serum antibodies to rat eye muscle (EMAB) in an enzyme linked immunosorbent assay and peripheral blood lymphocyte subsets by flow cytometry. Diplopia and periorbital edema markedly improved after treatment in 9 patients. Mean proptosis values and intraocular pressure measurements significantly decreased after pulse therapy. In 12 patients enlarged eye muscles significantly reduced in size after treatment, as determined by MRI. The overall ophthalmopathy index was improved from 4.8 +/- 2.4 to 2.5 +/- 1.6 at the end of pulse therapy (P < 0.01) and 2.4 +/- 1.5 six months after therapy (P < 0.01). Serum EMAB were detected in 8 out of 10 patients tested and their level significantly decreased after pulse therapy (from 3.3 +/- 1.4 to 2.5 +/- 1.2, P < 0.01). A significant increase in peripheral blood CD4+CD45RA+ cells was observed after pulse therapy. Increased numbers of CD11-CD8+ cells and decreased numbers of CD11+CD8++ cells were found prior to treatment and were normalized after pulse therapy. Our study indicates that methylprednisolone pulse therapy can be considered as a choice for the treatment of GO. The improvement in eye muscle involvement in these patients may be due to the effects of infused methylprednisolone on both humoral and cellular immune functions.

Adult↗

PubMed1993

FK506 inhibits phytohemagglutinin-, but not interferon-gamma-, induced HLA-DR antigen expression and accessory cell function on primary cultured human thyroid cells.

We investigated the effects of FK506, a novel immunosuppressive agent, on the phytohemagglutinin (PHA) or interferon-gamma (IFN-gamma)-induced expression of HLA-DR antigen, accessory cell function and proliferation of primary cultured human thyroid cells. Primary cultured thyroid cells from patients with Graves' disease were incubated for 3 days with PHA in concentrations in the range 1-50 mg/l or with 200 kU/l of IFN-gamma, in the presence or absence of FK506. The surface expression of HLA-DR antigen was measured by flow cytometry. Accessory cell function of thyroid cells was assessed by the incorporation of [3H]thymidine to T cells in the presence of 0.1-1.0 micrograms/l staphylococcus enterotoxin B (SEB). The proliferation of thyroid cells was determined from [3H]thymidine incorporation assays. FK506 inhibited the induction of HLA-DR antigen expression by PHA on thyroid cells in a dose-dependent manner, but did not inhibit that by IFN-gamma. Polyclonal anti-IFN-gamma antibody partly inhibited the PHA-induced HLA-DR antigen expression on thyroid cells. Phytohemagglutinin enhanced the SEB-mediated accessory cell function of thyroid cells. FK506 inhibited the accessory cell function induced by PHA. FK506 alone did not directly affect the thyroid cell proliferation, although it ameliorated the thyroid cell growth suppressed by PHA. Our data suggest that FK506 suppresses the HLA-DR antigen expression induced by PHA and the subsequent accessory cell function on thyroid cells via the inhibition of T lymphocytes present in the primary culture.

Antigen-Presenting Cells↗

PubMed1993

Inhibitory effects of nicotinamide on intercellular adhesion molecule-1 expression on cultured human thyroid cells.

We investigated the effects of nicotinamide and 3-aminobenzamide (3-AB), inhibitors of poly (ADP ribose) synthetase, on phytohaemagglutinin (PHA)- or interferon-gamma (IFN-gamma)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured thyroid cells from patients with Graves' disease. Primary cultured thyroid cells were incubated for 3 days with IFN-gamma (10-800 U/ml) or PHA (1-50 micrograms/ml) in the presence of nicotinamide, 3-AB, superoxide dismutase or catalase. The surface expression of ICAM-1 was measured by flow cytometry. Nicotinamide and 3-AB dose-dependently inhibited the induction of ICAM-1 expression by IFN-gamma or PHA on thyroid cells. Neither catalase nor superoxide dismutase, which are free-radical scavengers, inhibited the expression of ICAM-1 on thyroid cells. Our data suggest that the mechanism of the suppression of ICAM-1 expression on thyroid cells by nicotinamide is not likely to be due to the free radical scavenging. Further studies are indicated to elucidate whether the inhibition of ICAM-1 by these drugs may result in the suppression of autoimmune reaction in the thyroid gland.

Antigens, CD↗

PubMed1992

[Prediction for effectiveness of steroid pulse therapy by MRI in Graves' ophthalmopathy].

Fifteen patients with Graves' ophthalmopathy (GO) were treated with intravenous methylprednisolone (steroid pulse therapy, 1g daily for 3 days a week, 2-4 times) and followed up by ophthalmological assessment and magnetic resonance imaging (MRI). The signal intensity of enlarged eye muscle and retrobulbar fat was examined with MRI at 0.5T with short inversion time inversion recovery (STIR) sequences. The signal intensity of eye muscle and retrobulbar fat tissue in STIR was evaluated as the ratio to cerebral substantia alba (signal intensity ratio). The thickness of enlarged eye muscle was measured by T1-weighted coronal images. The signal intensity ratios of enlarged eye muscle of GO patients were significantly higher than those of eight normal subjects. Although the signal intensity ratios of muscle and retrobulbar fat before therapy were not related to the severity of clinical findings of GO assessed by ophthalmopathy index, the initial signal intensity ratios of eye muscle and retrobulbar fat of ten patients with improved clinical findings of GO after steroid pulse therapy tended to be higher than those of five patients without improvement by the therapy. After the therapy the signal intensity ratios of muscle and retrobulbar fat were significantly decreased in ten patients with favorable response. Our data suggested that high signal intensity in STIR may reflect edema caused by acute inflammation associated with GO. In conclusion, MRI may be a useful tool for determining the indication and prognosis of steroid pulse therapy. We strongly recommend measuring the signal intensity of eye muscle as well as muscle thickness in MRI to evaluate the activity of GO.

Adipose Tissue↗

PubMed1992

Inhibitory effects of nicotinamide on recombinant human interferon-gamma-induced intercellular adhesion molecule-1 (ICAM-1) and HLA-DR antigen expression on cultured human endothelial cells.

Intercellular adhesion molecule-1 (ICAM-1), HLA-A, B, C and HLA-DR antigen on endothelial cells (EC) play important roles in the development of inflammatory processes in autoimmune disorders. In the present study, we investigated the effect of nicotinamide, an inhibitor of poly(ADP ribose) synthetase, on interferon-gamma (IFN gamma)-induced ICAM-1 and HLA-DR antigen expression on the surface of cultured human umbilical vein endothelial cells, assessed by flow cytometry, and EC proliferation by counting cell numbers and [3H]thymidine incorporation assays. Nicotinamide dose-dependently inhibited the IFN-gamma-induced ICAM-1 and HLA-DR antigen expression, but not HLA-A, B, C antigen expression on cultured EC. Furthermore, nicotinamide significantly inhibited endothelial cell proliferation, as assessed by [3H]thymidine incorporation assay. Our findings suggest that nicotinamide may suppress mononuclear cell infiltration, antigen presentation and angiogenesis in the lesions of autoimmune disorders by reducing both IFN gamma-induced ICAM-1 and HLA-DR antigen expression on EC, and EC proliferation. Therefore, nicotinamide can be used for the treatment and prevention of the development of autoimmune disorders.

Antigens, CD↗

PubMed1992

Role of magnetic resonance imaging in thyroid-associated ophthalmopathy: its predictive value for therapeutic outcome of immunosuppressive therapy.

To investigate the efficacy of magnetic resonance imaging (MRI) in the assessment of thyroid-associated ophthalmopathy (TAO), 51 patients with TAO were evaluated by ophthalmologic examinations and MRI at 0.5 T. Thickness of extraocular muscles (EM) was measured by T1-weighted image. Signal intensities of EM and orbital connective tissue (OCT) were measured by short inversion time inversion recovery (STIR) image and expressed as a ratio by comparison to the signal intensity of cerebral substantia alba (SI, signal intensity ratio). Significant enlargement of one or more EM was observed in 86% of patients with TAO, and SI of EM (2.15 +/- 0.63, mean +/- SD) was significantly increased compared with control values (n = 16; 1.35 +/- 0.33; t test, p < 0.01). SI of OCT tended to be greater than that in the control group, although the difference was not significant. There was a significant positive correlation between thickness of EM and severity of ophthalmopathy, assessed as an ophthalmopathy index (p < 0.05). SI of neither EM nor OCT correlated with the severity of the eye disease. To investigate whether MRI findings could predict the outcome of methylprednisolone pulse therapy, we studied 23 patients with TAO who received this treatment. SI of EM and OCT in the 12 patients giving favorable responses were significantly greater than those in the 11 patients without good response (t test, p < 0.01). On the other hand, the thickness of eye muscles did not correlate with the outcome of treatment except for that of medial rectus muscle. There was a significant correlation between SI of EM and that of OCT (r = 0.78, p < 0.01), suggesting possible similar pathologic processes in these tissues in TAO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗