Biomedical subjects

Eijun Nishihara

Publications and source records attributed to Eijun Nishihara.

13 recordsLinked to original sources

PubMed2007

Expression of steroid receptor coactivator-1 is elevated during neuronal differentiation of murine neural stem cells.

The cell-lineage-specific fate of neural stem cells (NSCs) is defined by spatial and temporal gene expression regulated by various transcription factors and their coregulators, including coactivators and corepressors. To clarify the cellular distribution of the steroid receptor coactivator-1 (SRC-1), a ligand-dependent nuclear receptor coactivator, during neurogenesis, we examined the expression profiles of SRC-1 during the proliferation and differentiation in culture of NSCs derived from the ganglionic eminence of mouse embryos. We found that SRC-1 was rarely expressed in proliferating cells and multipotent precursors with the typical characters of NSCs. Under conditions that promote the differentiation of NSCs, both the SRC-1 transcript and protein levels were elevated and the population of SRC-1-positive cells was found to be higher in the mature neurons than in the immature neurons. In contrast, SRC-1 expression was rarely localized in the glial lineage cells, including astrocytes and oligodendrocytes. These results indicate that SRC-1 expression accompanies the appearance of neuronal-fate-committed cells derived from multipotent NSCs and is preferentially expressed in neuronal lineage cells during the differentiation of NSCs.

Analysis of Variance↗

PubMed2006

Effect of levo-thyroxine replacement on non-high-density lipoprotein cholesterol in hypothyroid patients.

CONTEXT: Recently, non-high-density lipoprotein cholesterol (non-HDL-C), a measure of total cholesterol minus HDL-C, has emerged as a predictor of cardiovascular disease. OBJECTIVE: We evaluated the effect of L-T4 replacement on non-HDL-C levels in patients with primary hypothyroidism. METHODS: Thirteen patients with overt hypothyroidism and 26 patients with subclinical hypothyroidism participated in the study. The lipid profiles, including non-HDL-C, were measured in patients with hypothyroidism before and 3 months after L-T4 replacement was started. RESULTS: After L-T4 replacement, the serum concentrations of all lipoproteins, exclusive of lipoprotein (a) [Lp(a)], were significantly decreased in patients with overt hypothyroidism. In patients with subclinical hypothyroidism, the serum concentrations of total cholesterol, non-HDL-C, remnant-like particle cholesterol, and apolipoprotein B (Apo B) were significantly decreased, whereas no significant changes in the serum concentrations of low-density lipoprotein cholesterol, HDL-C, triglycerides, apolipoprotein A-I, and Lp(a) were observed. In all 39 patients, the reduction in the non-HDL-C levels correlated with the reduction in the low-density lipoprotein cholesterol, remnant-like particle cholesterol, and Apo B levels. However, the reduction in the non-HDL-C levels did not correlate with the reduction in the HDL-C, Lp(a), and apolipoprotein A-I levels. CONCLUSIONS: This study is the first to show that L-T4 replacement may reduce serum concentrations of non-HDL-C in patients with hypothyroidism. The study also suggests that such altered serum concentrations of non-HDL-C in hypothyroidism may be related to the disturbed metabolism of low-density lipoprotein, remnant lipoprotein, and Apo B.

Adult↗

PubMed2006

Sporadic congenital hyperthyroidism due to a germline mutation in the thyrotropin receptor gene (Leu 512 Gln) in a Japanese patient.

Constitutively activating thyrotropin receptor (TSHR) germline mutations have been identified as a molecular cause of congenital hyperthyroidism. We here describe a Japanese woman who had presented with severe hyperthyroidism and advanced bone age as a neonate. She underwent neurosurgical intervention for craniosynostosis, and presented with perodactylia and mild mental retardation with hydrocephalus. Hyperthyroidism has been refractory to antithyroid drug therapy in the absence of antithyrotropin receptor antibodies during follow-up of 20 years, resulting in an enlarged goiter. Analysis of the patient's genomic DNA showed a heterozygous thymine-to-adenine point mutation in exon 10 of TSHR at position 1535 which was not present in the parents' DNA. This mutation, changing leucine to glutamine in codon 512 in the third transmembrane region, was previously identified as a somatic mutation in toxic thyroid nodules and was shown to increase basal cAMP production in vitro. To our knowledge, this is the first report of a germline mutation of TSHR causing sporadic congenital nonautoimmune hyperthyroidism in a Japanese patient.

Adult↗

PubMed2006

Two-day thionamide withdrawal prior to radioiodine uptake sufficiently increases uptake and does not exacerbate hyperthyroidism compared to 7-day withdrawal in Graves' disease.

The appropriate period of antithyroid drug (ATD) discontinuation before radioiodine therapy is the most critical problem in Graves' disease patients under going treatment with ATD. To determine the optimal period that does not alter the outcome of radioiodine therapy or exacerbate hyperthyroidism, we compared serum FT4 levels at radioiodine uptake (RAIU) and therapy outcomes between a 2-day withdrawal group and 7-day withdrawal group. We prospectively recruited 43 patients for the 2-day withdrawal protocol and retrospectively reviewed 49 patients treated with radioiodine following the protocol of 7-day withdrawal. There was no significant difference in RAIU between the 2 groups. The mean serum FT4 level measured on the first day of 24-h RAIU of the 7-day group was significantly higher than that in the 2-day group. There were no significant differences in the outcomes at each point (6 months, 1 year, and 2 years after therapy) between the 2 groups. Our results indicated that withdrawal of ATD for 2 days is superior to 7 days in that 2 days discontinuation did not exacerbate hyperthyroidism. In order to prevent serum thyroid hormone increase after ATD withdrawal and radioiodine therapy, a 2-day ATD withdrawal period before radioiodine therapy may be useful for high-risk patients such as the elderly and patients with cardiac complications. We believe that the 2-day ATD withdrawal method may be useful for patients undergoing treatment with ATD who are to undergo radioiodine therapy.

Adult↗

PubMed2006

A case of hypothyroid Graves' disease following external radiation therapy to the cervical region.

A case of hypothyroid Graves' disease occurred following external radiation therapy to the cervical region is described. Severe hypothyroidism developed in a 56-year-old man 6 months after external radiation therapy for submandibular cancer. Serological evaluation of thyroid autoimmunity revealed the presence of antithyroid antibodies and thyrotropin-binding inhibitory immunogloblins (TBII). Diplopia, limitation of downward gaze, and palpebral edema developed 2 years after levothyroxine replacement therapy. Ocular magnetic resonance imaging revealed marked hypertrophy of the bilateral extraocular muscles with signal hyperintensity on T2-weighted images. This infiltrative ophthalmopathy showed marked improvement after additional treatment with high-dose methylprednisolone and orbital radiation, in parallel with a decrease in TBII. These results suggest that radiation-associated thyroidal injury might be associated with the etiology of hypothyroid Graves' disease.

Carcinoma, Squamous Cell↗

PubMed2006

Four cases of Graves' disease which developed after painful Hashimoto's thyroiditis.

We report four cases of Graves' disease that developed after painful Hashimoto's thyroiditis. All were middle-aged women, who had high titers of anti-thyroid antibodies and thyrotoxicosis at the onset of painful Hashimoto's thyroiditis. After 2 to 7 years, they developed Graves' disease with positive antibody against the thyrotropin receptor. Their clinical courses of Graves' disease went favorably due to the treatment with antithyroid drug or radioactive iodine therapy. Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's thyroiditis and is one form of destructive thyroiditis. Thyroid damage due to painful Hashimoto's thyroiditis may be associated with the development of Graves' disease.

Antithyroid Agents↗

PubMed2005

Vitamin E prevents the neuronal cell death by repressing cyclooxygenase-2 activity.

The accumulation of damage caused by oxidative stress exacerbates cell death in many neurodegenerative diseases. We evaluated the mechanism of neuronal cell death raised by glutamate-induced toxicity, using the immortalized mouse hippocampal cell line HT-22. Our results showed that vitamin E prevented glutamate-induced cell death, accompanied by the decline of cyclooxygenase-2 expression confirmed by reverse transcriptase polymerase chain reaction and immunocytochemistry. Moreover, the neuroprotection was still effective even when vitamin E was supplied after glutamate treatment. The decline of cyclooxygenase-2 activity was also highly correlated with the neural protective effect against glutamate-induced toxicity. These results represent new insights about the timing of vitamin E supplementation after toxic stimulation and one mechanism by which vitamin E could prevent neuronal cell death by controlling cyclooxygenase-2 activity.

Animals↗

PubMed2005

Acute suppurative thyroiditis after fine-needle aspiration causing thyrotoxicosis.

A case of thyrotoxicosis caused by acute suppurative thyroiditis after repeated fine-needle aspiration (FNA) is described. A 39-year-old woman with atopic dermatitis showed rapid enlargement of a left thyroid cyst after a third FNA. She had a high fever, painful swelling of the left thyroid, and elevated thyroid hormone levels. Ultrasonography revealed abscess formation in the left thyroid cyst. The cytologic examination of an FNA specimen showed abundant neutrophils, and culture of the aspirate yielded Staphylococcus aureus. Because antibiotic treatment for 1 month failed to improve the inflammatory findings, the patient subsequently underwent left thyroid lobectomy, which resulted in the normalization of thyroid function and the resolution of inflammation. Thyroid infection had possibly been induced by needle-track seeding, because atopic skin favors colonization by S. aureus because of local immunologic deficiency. FNA is a useful and safe technique for aspirating fluid from thyroid cysts, but special care is required in patients with atopic dermatatis to avoid bacterial infection.

Adult↗

PubMed2005

Successful use of iodine and levothyroxine to treat Graves' disease in a pregnant patient with allergy to antithyroid drugs and high thyrotropin-binding inhibitor immunoglobulin after radioiodine therapy.

High titer of thyrotropin-binding inhibitor immunoglobulin (TBII) in patients with Graves' disease can cause fetal hyperthyroidism during pregnancy. Prevention of fetal hyperthyroidism by administration of antithyroid drug (ATD) and levothyroxine (LT(4)) to pregnant patients who previously received ablative therapy has been reported. We administered iodine and LT(4) to a patient during gestation, because she had a severe adverse reaction to ATD. Although gestation proceeded normally, the infant showed transient neonatal hyperthyroidism right after birth. We believe that the fetus would have developed hyperthyroidism if we had not administered iodine to the mother. Administration of iodine and LT(4) to a pregnant patient with Graves' disease showing a high TBII after ablative therapy should be considered in rare patients with allergy to ATD.

Adult↗

PubMed2005

Effect of high dose methylprednisolone pulse therapy followed by oral prednisolone administration on the production of anti-TSH receptor antibodies and clinical outcome in Graves' disease.

Little is known about the immunosuppressive effect of glucocorticoids on TSH receptor antibodies. We observed the long-term prognosis and serum TSH binding inhibitor immunoglobulin (TBII) levels in patients with Graves' ophthalmopathy who had received intravenous methylprednisolone pulse therapy (pulse therapy) followed by oral prednisolone administration in order to ascertain how long the immunosuppressive effect of glucocorticoids continued. This is the first report on the effect of pulse therapy on Graves' disease outcome. We observed 67 patients who were treated by antithyroid drugs (ATD) alone for 2 years after pulse therapy. TBII was evaluated before and 3, 6, 12, 18, and 24 months after pulse therapy. The mean TBII decreased significantly 3 months after pulse therapy (p<0.001), and was maintained until 24 months. There were 24 patients whose TBII was positive (>15%) at 24 months, in whom the mean TBII decreased significantly 3 to 6 months after pulse therapy (p<0.001), but increased again at 12 to 24 months (p<0.05). Thus, the immunosuppressive effect of glucocorticoids may be lost at 12 months after pulse therapy in these patients. The remission rate in the pulse therapy group was 40.98%, and that of the control patient group was 48.57%. There was no significant difference between the two. These results suggest that the immunosuppressive effect of pulse therapy was temporary, and that pulse therapy did not increase remission rate of Graves' disease.

Administration, Oral↗

PubMed2004

Nuclear receptor coregulators are new players in nervous system development and function.

Steroid/thyroid hormones and their cognate nuclear receptors (NRs) play important roles in nervous system development and function. The spatial and temporal gene expression that is regulated by NRs in the nervous system requires transcriptional intermediary coregulators, designated as coactivators and corepressors. These coregulators enhance or repress transcriptional activity of NRs and modulate their target gene transcription. Recent progress has largely advanced our understanding of the molecular mechanisms by which NR coregulators function in the nervous system. This article summarizes our current knowledge about the molecular mechanisms, expression patterns, and biological functions of NR coactivators, such as the p160 steroid receptor coactivator family, CBP, p300, BRG1, TRAP220, PGC-1alpha, ERAP140, NIX1, and E6-AP, as well as corepressors such as NCoR and SMRT. Accumulated findings suggest that the functional spectrum of NR coregulators is much broader than was initially speculated, and these coregulators likely contribute to many physiological aspects of nervous system development and function.

Animals↗

PubMed2003

Effects of loss of steroid receptor coactivator-1 on the skeletal response to estrogen in mice.

Steroid receptor coactivator (SRC)-1 is an important nuclear receptor coactivator that enhances estrogen (E) action in many tissues, but its role in mediating E effects on bone is unknown. Thus, we assessed the skeletal response to ovariectomy (ovx) and E replacement in SRC-1 knockout (KO) mice compared with wild-type (WT) littermates. Bone mineral density was measured by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography at baseline and after 2 months of sham surgery, ovx, or ovx plus E replacement. Microcomputed tomography and bone histomorphometry were also performed at the end of the study. Both WT and SRC-1 KO mice lost bone at multiple sites after ovx; however, although an estradiol (E(2)) dose of 10 microg/kg.d completely prevented loss of cancellous bone (at the lumbar spine and tibial metaphysis) in the WT mice, it was entirely ineffective in preventing cancellous bone loss at these sites in the SRC-1 KO mice. This E(2) dose was, however, equally effective on cortical bone in the tibia in the SRC-1 KO and WT mice. Moreover, a 4-fold higher dose of E(2) was able to overcome the deficit in E action in cancellous bone in the SRC-1 KO mice. These findings establish that, in mice, loss of SRC-1 leads to skeletal resistance to E predominantly in cancellous bone.

Absorptiometry, Photon↗

PubMed2003

SRC-1 null mice exhibit moderate motor dysfunction and delayed development of cerebellar Purkinje cells.

Hormones and nuclear receptors (NRs) play important roles in brain development and function. The recently identified steroid receptor coactivator (SRC) family contains three homologous members that can enhance transcriptional activities of NRs and certain non-NR transcription factors. To study the role of SRC-1 in brain development and function, we examined the spatial and temporal expression patterns of SRC-1 and characterized the phenotypes of brain development and function in SRC-1 knock-out (SRC-1(-)/-) mice. In the adult mouse brain, SRC-1 is highly expressed in the olfactory bulb, hippocampus, piriform cortex, amygdala, hypothalamus, cerebellum, and brainstem. Multiple behavioral tests revealed that SRC-1(-)/- mice exhibit normal hippocampal function but moderate motor dysfunction. The behavior phenotypes correlate with the spatial distribution of the SRC family members. In most brain structures where SRC-1 is expressed, SRC-2 is expressed at lower levels; however, SRC-3 mRNA is detectable only in the hippocampus. In the adult cerebellum, Purkinje cells (PCs) preferentially express SRC-1 over SRC-2, but SRC-2 mRNA is slightly elevated in the SRC-1(-)/- PCs. During embryonic development, SRC-1 is expressed in the cerebellar primordium. SRC-2 is expressed in PCs after postnatal day (P) 10. Time course analysis revealed that the precursors of SRC-1(-)/- PCs were generated approximately 2 d later than wild-type precursor cells. A further delay in SRC-1(-)/- PC maturation was detected at the neonatal stage. The morphology and number of SRC-1(-)/- PCs were equivalent to wild type by P10; this timing correlated with the early expression of SRC-2 in the SRC-1(-)/- PCs. These results demonstrate that the relative levels of SRC expression are region specific, and the degree of overlapping expression may influence their functional redundancy. Disruption of SRC-1 specifically delays the PC development and maturation in early stages and results in moderate motor dysfunction in adulthood.

Animals↗