東北大学 · 生化学・遺伝学・分子生物学
高良清志教授の研究室は、脳血管障害における神経伝達物質の動態と脳血流量の関連を、マイクロダイアリシスとレーザー・ドップラー血流計測を用いて解明しています。特に、虚血状態下におけるグルタメートの放出機構や、発熱が脳保護に与える影響を動物モデルで解析しています。また、乳癌におけるエストロゲン受容体やアンドロゲン受容体の機能と関連するタンパク質（NUCB2、APPなど）の臨床的意義についても、免疫染色やin vitro実験を組み合わせて研究を進めています。
Figures are computed from collected data and may differ slightly.
We simultaneously measured neurotransmitter amino acids by the microdialysis technique and cortical CBF by laser-Doppler flowmetry in the ischemic penumbral cortex of rats subjected to 2-h normothermic (36.5-37.5 degrees C) transient middle cerebral artery (MCA) clip-occlusion. Brains were perfusion-fixed 3 days later and infarct volume measured. CBF (% of preischemic values) fell to 32 +/- 2% (mean +/- SD) during ischemia and rose to 157 +/- 68% during recirculation. Extracellular glutamate lev
Using microdialysis, we investigated the effect of hyperthermia on glutamate release in penumbral cortex of rats with 2 h of either normothermic (37 degrees C) or hyperthermic (39 degrees C) middle cerebral artery (MCA) occlusion. Penumbral blood flow (CBF) was measured by laser-Doppler flowmetry. CBF values (expressed as % preischemic values) in normothermic and hyperthermic groups were 24 +/- 11 (SD) and 24 +/- 16%, respectively, during ischemia and 102 +/- 81 and 147 +/- 79% during recirculat
The combinatorial approach, guided by the break points, is so simple and systematic that it can be used again in the future when revision of the grading scale becomes necessary after development of new and effective treatment modalities that improve patients' overall outcome.
Sex steroids play important roles in the development of many human breast carcinomas, and aromatase inhibitors are used for the anti-estrogen therapy. Recent studies have demonstrated that aromatase suppressed 5alpha-dihydrotestosterone (DHT) synthesis in breast carcinoma cells, but intratumoral concentration of androgens and its significance have not been reported in the breast carcinoma patients treated with aromatase inhibitors. Therefore, we examined androgen concentrations in breast carcino
It is well-known that estrogens immensely contribute to the progression of human breast carcinoma, but their detailed molecular mechanisms remain largely unclear. In this study, we identified nucleobindin 2 (NUCB2) as a gene associated with recurrence based on microarray data of estrogen receptor (ER)-positive breast carcinoma cases (n = 10), and subsequent in vitro study showed that NUCB2 expression was upregulated by estradiol in ER-positive MCF-7 cells. However, NUCB2 has not yet been examine
Amyloid precursor protein (APP) is a transmembrane protein that is highly expressed in brain tissue. Recently, APP has been implicated in some human malignancies, and its regulation by androgens has also been demonstrated. Such findings suggest the importance of APP in hormone-dependent breast carcinoma, but APP has not yet been examined in breast carcinoma tissues. Therefore, in this study, we examined the biological and clinical significance of APP in breast carcinoma using immunohistochemistr
Krüppel-like factor 5 (intestinal) or Krüppel-like factor 5 (KLF5) is a zinc finger-containing transcription factor and involved in important biological processes including cell proliferation and differentiation. However, clinical significance of KLF5 protein has remained largely unknown in breast cancer. Therefore, in this study, we immunolocalized KLF5 in 113 human breast carcinoma cases. KLF5 immunoreactivity was frequently detected in the nuclei of breast carcinoma cells, and median value of
We evaluated acute alterations of local cerebral perfusion following 30 min of transient right proximal middle cerebral artery (MCA) clip-occlusion in the rat and following two intervals of postischemic reperfusion. Local cerebral blood flow (lCBF) was assessed by [14C]iodoantipyrine autoradiography. Brain temperature was controlled at 35.5-36.5 degrees C throughout the experiment. We measured lCBF in four groups of rats: (a) sham-operated controls (n = 5), (b) following 30 min MCA occlusion (n
Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well a
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