The Keio Journal of Medicine

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(Pro)renin Receptor and Vacuolar H⁺−ATPase

Atsuhiro Ichihara

2012 年 61 巻 3 号 p. 73-78
発行日: 2012/09/25
公開日: 2012/10/03

DOIhttps://doi.org/10.2302/kjm.61.73

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The (pro)renin receptor [(P)RR] is a molecule that binds prorenin and renin in tissues, leading not only to their activation, but also carrying out intracellular signaling. As a key player in the tissue renin–angiotensin system, (P)RR activation plays an important role in the development of end-organ damage in hypertension and diabetes. One fragment of (P)RR is also known as ATP6AP2 because it is associated with vacuolar H⁺-ATPase (V-ATPase). V-ATPase is a multi-subunit proton pump involved in diverse and fundamental aspects of cellular physiology, including receptor-mediated endocytosis and recycling, processing of proteins and signaling molecules, membrane sorting and trafficking, and activation of lysosomal/autophagosomal enzymes. The role of (P)RR in the function of V-ATPase has been investigated in recent studies using conditional knockout mice. Furthermore, the novel function of (P)RR as an adaptor protein between the Wnt receptor complex and V-ATPase has been demonstrated. Thus, (P)RR is a multi-functional molecule that has complex structure and functionality. This review focuses on current insights into the possibility of (P)RR acting as a modulator of V-ATPase and future perspectives in translational research.

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Blood Cholesterol Level and Risk of Stroke in Community-based or Worksite Cohort Studies: A Review of Japanese Cohort Studies in the Past 20 years

Taichiro Tanaka, Tomonori Okamura

2012 年 61 巻 3 号 p. 79-88
発行日: 2012/09/25
公開日: 2012/10/03

DOIhttps://doi.org/10.2302/kjm.61.79

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Evidence of the causal relationship between hypercholesterolemia and coronary artery disease (CAD) has been established worldwide. However, little attention has been paid to the relationship between hypercholesterolemia and stroke, despite stroke being the most common cardiovascular disease in Japan. We therefore reviewed cohort studies that investigated this relationship in the Japanese population over the past 20 years, and compared their findings with clinical trials and cohort studies in Western countries. Fourteen cohort studies were carried out in Japan during this period. The number of subjects in the studies ranged from 1621 to 91,219 and the mean follow-up period ranged from 7.6 to 32 years. The majority of studies showed no association between hypercholesterolemia and total stroke. However, one report showed a positive association between low-density lipoprotein cholesterol and atherothrombotic cerebral infarction. The relationship between hypercholesterolemia and cerebral infarction may be modified by the proportion of atherothrombotic infarctions in the population surveyed. Randomized controlled trials on statins have shown a substantial reduction in cerebral infarction, and so the discrepancy between cohort studies and clinical trials requires further study. However, some studies have reported that subjects with low blood cholesterol are more susceptible to intracerebral hemorrhage. Two hypotheses have been proposed to explain this association between low cholesterol and intracerebral hemorrhage. First, low blood cholesterol may induce angionecrosis, possibly in combination with hypertension, and second, low blood cholesterol may reflect a poor nutritional status. Either way, further continuous research in various fields of medical science is required to clarify the overall effect of blood cholesterol on stroke in humans.

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ORIGINAL ARTICLE

Preimplant Factors Affecting Prostate D90 after Transperineal Interstitial Prostate Brachytherapy with Loose ¹²⁵I Seeds

Akitomo Sugawara, Jun Nakashima, Etsuo Kunieda, Hirohiko Nagata, Ryuic ...

2012 年 61 巻 3 号 p. 89-94
発行日: 2012/09/25
公開日: 2012/10/03

DOIhttps://doi.org/10.2302/kjm.61.89

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The dose received by 90% of the prostate volume (D90) is the key parameter of dosimetric analysis in prostate brachytherapy. The aim of this analysis was to identify preimplant factors affecting prostate D90 after transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds. We reviewed the records of 210 patients who underwent transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds for clinical T1/T2 prostate cancer at our institution. Patients who received supplemental external-beam radiation therapy were excluded. One hundred and nine patients (51.9%) received neoadjuvant hormonal therapy (NHT). One month after seed implantation, postimplant computed tomography and dosimetric analysis were performed. Univariate and multivariate analyses were carried out to identify preimplant factors affecting postimplant prostate D90. The postimplant prostate D90 values ranged from 123.3 to 234.1 Gy (mean ± standard error, 177.1 ± 1.4 Gy). Postimplant prostate D90 differed significantly between patients who had and had not undergone NHT (P = 0.001). In addition, simple regression analyses showed positive correlations with the estimated preimplant prostate D90, preimplant prostate volume by transrectal ultrasound (TRUS), total radioactivity, number of needles, and number of seeds. On stepwise multiple regression analysis, postimplant prostate D90 showed significant negative correlations with NHT and preimplant prostate volume by TRUS, and a significant positive correlation with total radioactivity. In conclusion, NHT, preimplant prostate volume by TRUS, and total radioactivity are significant preimplant factors affecting postimplant prostate D90 in prostate cancer patients treated with transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds.

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