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N Ishisaka

Publications and source records attributed to N Ishisaka.

5 recordsLinked to original sources

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↗

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↗

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↗

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↗

[Recording system for the scotopic threshold response].

The scotopic threshold response (STR) is a newly investigated component of the electroretinogram. Since the STR reflects post-photoreceptoral processing in the retina at intensities near absolute threshold, the STR would be a useful index to evaluate the rod pathway in the proximal retina. A conventional ERG setup, however, involves difficulties in STR recording. Therefore we constructed a new recording system for the purpose. The characteristics of the apparatus are as follows: 1) A diffusing sphere provides full-field stimuli ranging from a very dim light near absolute threshold to a very bright light. 2) A remote-control system for changing filters is used to avoid breakdown of the dark-adapted status. 3) A software artifact rejection routine is used to exclude responses influenced by eye movements and blinks. Using the apparatus we have examined the human STR and generally confirmed the previous findings.

Adult↗