57 results on '"Shigeatsu Hashimoto"'
Search Results
2. PS-R07-10: A MOTHER AND HER DAUGHTER CASES OF PRIMARY ALDOSTERONISM
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Yuhi Nemoto, Kazuya Honda, Koji Hasegawa, and Shigeatsu Hashimoto
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Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
3. PS-C37-4: COMPARISON OF A SALT CHECK SHEET WITH ESTIMATED URINARY SALT EXCRETION MEASUREMENT IN HYPERTENSIVES OF AIZU REGION IN TOHOKU AREA
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Rie Inomata and Shigeatsu Hashimoto
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Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
4. Influence of post-disaster evacuation on incidence of hyperuricemia in residents of Fukushima Prefecture: the Fukushima Health Management Survey
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Kanako Okazaki, Tetsuya Ohira, Yukihiko Kawasaki, Atsushi Takahashi, Shigeatsu Hashimoto, Hitoshi Suzuki, Shingo Fukuma, Akira Ohtsuru, Akira Sakai, Masato Nagai, Hiroaki Satoh, Shunichi Yamashita, Seiji Yasumura, Shunichi Fukuhara, Hitoshi Ohto, Mitsuaki Hosoya, Gen Kobashi, and Kenji Kamiya
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Adult ,Male ,medicine.medical_specialty ,Waist ,Physiology ,Hyperuricemia ,Logistic regression ,Body Mass Index ,Sex Factors ,Japan ,Physiology (medical) ,Environmental health ,Internal medicine ,Rescue Work ,medicine ,Fukushima Nuclear Accident ,Humans ,Longitudinal Studies ,Triglycerides ,Aged ,Aged, 80 and over ,business.industry ,Incidence ,Incidence (epidemiology) ,Cholesterol, HDL ,nutritional and metabolic diseases ,Cholesterol, LDL ,Odds ratio ,Middle Aged ,medicine.disease ,Health Surveys ,Confidence interval ,Uric Acid ,Disaster ,Nephrology ,And life style ,Female ,Original Article ,Disaster Victims ,Waist Circumference ,business ,Evacuation ,Body mass index ,Cohort study - Abstract
Aim After the Great East Japan Earthquake, over 160,000 residents in Fukushima Prefecture were forced to evacuate the area around the Fukushima Daiichi power plant following nuclear accident there. Health problems in these evacuees have since become a major issue. We have examined the association between evacuation and incidence of hyperuricemia among residents in Fukushima. Methods We conducted a cohort study of residents aged 40–90 years without hyperuricemia at the time of the Fukushima disaster. Among 8173 residents who met the inclusion criteria before the disaster, 4789 residents (men: 1971, women: 2818; follow-up duration: 1.38 years; and follow-up rate: 58.6%) remained available for follow-up examinations at the end of March 2013. The main endpoint was incidence of hyperuricemia, defined by the Japanese committee guidelines, using local health data from before and after the disaster. We divided participants by evacuation status and compared outcomes between groups. Using a logistic regression model, we estimated the odds ratio for incidence of hyperuricemia, adjusting for potential confounders, age, gender, waist circumference, physical activity, and alcohol consumption. Results Incidence of hyperuricemia was higher in evacuees (men 10.1%; women 1.1%) than in non-evacuees (men 7.4%, women 1.0%). Evacuees had higher body mass index, waist circumference, triglycerides, LDL-cholesterol, fasting plasma glucose, HbA1c, and lower HDL-cholesterol after the disaster than non-evacuees. We found that evacuation was associated with incidence of hyperuricemia (adjusted odds ratio: 1.38; 95% confidence interval: 1.03–1.86). Conclusion This is the first study to demonstrate an association between evacuation after a disaster and increased incidence of hyperuricemia.
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- 2020
5. Effects of Psychological and Lifestyle Factors on Metabolic Syndrome Following the Fukushima Daiichi Nuclear Power Plant Accident: The Fukushima Health Management Survey
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Yukihiko Kawasaki, Tetsuya Ohira, Atsushi Takahashi, Junichiro James Kazama, Kazuyuki Watanabe, Kenji Kamiya, Shigeatsu Hashimoto, Akira Sakai, Hirooki Yabe, Hitoshi Ohto, Kanako Okazaki, Hironori Nakano, Masaharu Maeda, Seiji Yasumura, Akira Ohtsuru, Mitsuaki Hosoya, Fumikazu Hayashi, Hiromasa Ohira, and Michio Shimabukuro
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Adult ,Male ,030204 cardiovascular system & hematology ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Environmental health ,Internal Medicine ,Medicine ,Fukushima Nuclear Accident ,Humans ,Life Style ,Aged ,Metabolic Syndrome ,Health management system ,Post-traumatic stress disorder ,business.industry ,Biochemistry (medical) ,Psychological distress ,Middle Aged ,Radiation Exposure ,medicine.disease ,Lifestyle ,Mental health ,Health Surveys ,Fukushima daiichi ,Lifestyle factors ,Cross-Sectional Studies ,Drinking Status ,Disaster ,Nuclear Power Plants ,Original Article ,Female ,Metabolic syndrome ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,Stress, Psychological ,Follow-Up Studies - Abstract
Aim The Fukushima Daiichi Nuclear Power Plant accident dramatically changed the lifestyle of residents who lived near the plant. We evaluated the association of metabolic syndrome (MetS) with specific lifestyle- and disaster-related factors in residents following the accident. Methods This cross-sectional study included 20,920 residents who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey from June 2011 to March 2012. Associations between MetS and lifestyle- and disaster-related factors, including psychological distress (post-traumatic stress disorder [PTSD]), were estimated using logistic regression analysis, adjusted for demographic and lifestyle factors, in 2019. Results MetS was present in 30.4% of men and 11.5% of women. There were significant differences in smoking, drinking status, and PTSD prevalence between subjects with and without MetS. Multivariable logistic regression analysis showed that age, quitting smoking, and low physical activity were significantly associated with MetS. Moreover, PTSD and light to moderate drinking were also significantly associated with MetS in women. Conclusions Lifestyle- and disaster-related factors, including PTSD, were associated with MetS among subjects who lived near the Fukushima Daiichi Nuclear Power Plant accident.
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- 2020
6. Renal impairment is closely associated with plasma aldosterone concentration in patients with primary aldosteronism
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Akiyuki Kawashima, Masakatsu Sone, Nobuya Inagaki, Yoshiyu Takeda, Hiroshi Itoh, Isao Kurihara, Hironobu Umakoshi, Takamasa Ichijo, Takuyuki Katabami, Norio Wada, Yoshihiro Ogawa, Junji Kawashima, Megumi Fujita, Shozo Miyauchi, Shintaro Okamura, Tomikazu Fukuoka, Toshihiko Yanase, Shoichiro Izawa, Yuichiro Yoshikawa, Shigeatsu Hashimoto, Masanobu Yamada, Tatsuya Kai, Tomoko Suzuki, and Mitsuhide Naruse
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Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Urology ,Renal function ,030209 endocrinology & metabolism ,Essential hypertension ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Primary aldosteronism ,Risk Factors ,Internal medicine ,Hyperaldosteronism ,medicine ,Humans ,Aldosterone ,Stroke ,Aged ,Retrospective Studies ,Kidney ,Proteinuria ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Cross-Sectional Studies ,Blood pressure ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Female ,Kidney Diseases ,medicine.symptom ,business ,Biomarkers - Abstract
Objective Several clinical studies have reported that renal impairments are sometimes observed in patients with primary aldosteronism (PA). We analyzed the prevalence of renal impairments in PA patients and identified parameters that increase the risk for them. Design This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan PA study (JPAS). Data were also collected from patients with essential hypertension (EHT). Methods We compared the prevalences of proteinuria and lowered estimated glomerular filtration rate (eGFR) between patients with PA and age, sex, blood pressure and duration of hypertension-matched patients with EHT. We also performed logistic regression analysis to identify parameters that increase the risk for these renal impairments. Results Among 2366 PA patients, the prevalences of proteinuria and lowered eGFR were 10.3 and 11.6%, respectively. The prevalence of proteinuria was significantly higher in PA patients than matched-EHT patients (16.8 vs 4.4%), whereas there was no significant difference in the prevalence of lowered eGFR (17.2 vs 15.0%). The logistic regression analysis also showed that the plasma aldosterone concentration (PAC) significantly increases the risk of proteinuria and lowered eGFR, independent of other known risk factors. Conclusion Plasma aldosterone levels are closely associated with renal impairment in patients with PA. This is contrast to our earlier finding that the PAC was not itself linearly associated with cardiovascular events such as stroke or ischemic heart disease. The mechanism underlying the kidney damage in patients with PA may differ from that affecting the cardiovascular system.
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- 2019
7. Correlation Between Lateralization Index of Adrenal Venous Sampling and Standardized Outcome in Primary Aldosteronism
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Hirotaka Shibata, Junji Kawashima, Nobuya Inagaki, Koichi Yamamto, Takamasa Ichijo, Hiroshi Itoh, Tatsuya Kai, Takanobu Yoshimoto, Toshihiko Yanase, Norio Wada, Maki Yokomoto-Umakoshi, Shoichiro Izawa, Kohei Kamemura, Shigeatsu Hashimoto, Yoshihiro Ogawa, Yui Shibayama, Shozo Miyauchi, Masakatsu Sone, Mika Tsuiki, Atsushi Ogo, Takashi Kawamura, Yuichiro Yoshikawa, Michio Otsuki, Yuichi Matsuda, Katsutoshi Takahashi, Hironobu Umakoshi, Mitsuhide Naruse, Isao Kurihara, Yoneda Takashi, Tomikazu Fukuoka, Masanobu Yamada, Yoshiyu Takeda, Takuyuki Katabami, Kenji Ashida, Yuichi Fujii, Minemori Watanabe, Shintaro Okamura, Tomoko Suzuki, and Hiroki Kobayashi
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Outcome (game theory) ,Unilateral disease ,Lateralization of brain function ,Correlation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Primary aldosteronism ,Internal medicine ,medicine ,Adrenal ,Clinical Research Articles ,aldosterone ,primary aldosteronism ,Aldosterone ,business.industry ,Confounding ,medicine.disease ,Adrenal venous sampling ,chemistry ,Cardiology ,adrenal venous sampling ,business - Abstract
Objectives The aim of this study was to investigate the impact of adrenal venous sampling (AVS) lateralization cutoffs on surgical outcomes. Patients and Methods Cosyntropin-stimulated AVS was used to guide surgical management of 377 patients with primary aldosteronism (PA) who were evaluated 6 months after surgery. Main Outcome Measures The proportion of patients that achieved clinical benefit and complete biochemical success based on the AVS aldosterone lateralization index (LI) was determined. Results Clinical benefit was achieved in 29 of 47 patients with an LI between 2 and 4, in 66 of 101 with an LI between 4 and 10, and in 158 of 203 with an LI > 10 (P < 0.01 for trend). Complete biochemical success was achieved in 27 of 42 with an LI between 2 and 4, in 60 of 76 with an LI between 4 and 10, and in 127 of 155 with an LI > 10 (P = 0.024 for trend). After adjustment for confounders and using those patients with an LI between 2 and 4 as a reference, a clinical benefit was associated only with those with an LI > 10 (OR, 2.30; 95% CI, 1.03 to 5.16), whereas complete biochemical success was associated with those with an LI between 4 and 10 (OR, 2.83; 95% CI, 1.14 to 7.01) or LI > 10 (OR, 3.55; 95% CI, 1.47 to 8.55). Conclusions Difference of clinical outcome was relatively small when strict LI diagnostic threshold was used; biochemical cure was sufficiently achieved when an LI > 4 was used. Our study by standardized outcome measures validated that an LI > 4 may be appropriate for determining unilateral disease in PA., We investigated the impact of AVS lateralization cutoffs on surgical outcome by standardized measures and validated that an LI > 4 is appropriate to determine unilateral disease in PA.
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- 2018
8. Prevalence of Cardiovascular Disease and Its Risk Factors in Primary Aldosteronism
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Megumi Fujita, Tomoko Suzuki, Tomikazu Fukuoka, Hironobu Umakoshi, Masakatsu Sone, Hirotaka Shibata, Michio Otsuki, Junji Kawashima, Yuichi Fujii, Katsutoshi Takahashi, Nobuya Inagaki, Takuyuki Katabami, Takamasa Ichijo, Yoshiyu Takeda, Shoichiro Izawa, Yasushi Tanaka, Shigeatsu Hashimoto, Isao Kurihara, Mitsuhide Naruse, Takashi Kawamura, Yuichi Matsuda, Shozo Miyauchi, Toshinari Yamasaki, Norio Wada, Yoshihiro Ogawa, Nagahama Study, Takanobu Yoshimoto, Osamu Ogawa, Kohei Kamemura, Yui Shibayama, Koichi Yamamoto, Atsushi Ogo, Mika Tsuiki, Youichi Ohno, Hiroshi Itoh, Minemori Watanabe, Toshihiko Yanase, Fumihiko Matsuda, Yasuharu Tabara, Hiroki Kobayashi, Shintaro Okamura, and Takashi Yoneda
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,030209 endocrinology & metabolism ,Comorbidity ,030204 cardiovascular system & hematology ,Essential hypertension ,Severity of Illness Index ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,Age Distribution ,0302 clinical medicine ,Primary aldosteronism ,Japan ,Risk Factors ,Internal medicine ,Hyperaldosteronism ,Prevalence ,Internal Medicine ,medicine ,Humans ,Registries ,cardiovascular diseases ,Myocardial infarction ,Sex Distribution ,Aldosterone ,Stroke ,Aged ,Retrospective Studies ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Survival Analysis ,chemistry ,Cardiovascular Diseases ,Heart failure ,Cardiology ,Female ,business ,Follow-Up Studies - Abstract
There have been several clinical studies examining the factors associated with cardiovascular disease (CVD) in patients with primary aldosteronism (PA); however, their results have left it unclear whether CVD is affected by the plasma aldosterone concentration or hypokalemia. We assessed the PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the prevalence of CVD among patients with PA with that among age-, sex-, and blood pressure-matched essential hypertension patients and participants with hypertension in a general population cohort. We also performed binary logistic regression analysis to determine which parameters significantly increased the odds ratio for CVD. Of the 2582 patients with PA studied, the prevalence of CVD, including stroke (cerebral infarction, cerebral hemorrhage, or subarachnoid hemorrhage), ischemic heart disease (myocardial infarction or angina pectoris), and heart failure, was 9.4% (stroke, 7.4%; ischemic heart disease, 2.1%; and heart failure, 0.6%). The prevalence of CVD, especially stroke, was higher among the patients with PA than those with essential hypertension/hypertension. Hypokalemia (K + ≤3.5 mEq/L) and the unilateral subtype significantly increased adjusted odds ratios for CVD. Although aldosterone levels were not linearly related to the adjusted odds ratio for CVD, patients with plasma aldosterone concentrations ≥125 pg/mL had significantly higher adjusted odds ratios for CVD than those with plasma aldosterone concentrations
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- 2018
9. The impact of evacuation on the incidence of chronic kidney disease after the Great East Japan Earthquake: The Fukushima Health Management Survey
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Akira Sakai, Tetsuya Ohira, Hitoshi Suzuki, Kotaro Ozasa, Shigeatsu Hashimoto, Atsushi Takahashi, Gen Kobashi, Mitsuaki Hosoya, Hiroaki Shishido, Yoshihiro Sugiura, Masafumi Abe, Yukihiko Kawasaki, Yoshimitsu Hayashi, Akira Ohtsuru, Masato Nagai, Seiji Yasumura, Junichiro James Kazama, Hiroaki Satoh, and Hideto Takahashi
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Male ,medicine.medical_specialty ,Earthquake ,Physiology ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,Physiology (medical) ,Chronic kidney disease ,medicine ,Fukushima Nuclear Accident ,Humans ,030212 general & internal medicine ,Risk factor ,Renal Insufficiency, Chronic ,Aged ,Proportional hazards model ,business.industry ,Incidence (epidemiology) ,Incidence ,Hazard ratio ,Middle Aged ,medicine.disease ,Confidence interval ,female genital diseases and pregnancy complications ,Disaster ,Nephrology ,Hypertension ,Original Article ,Female ,business ,Nuclear powerplant ,Evacuation ,Dyslipidemia ,Kidney disease ,Cohort study - Abstract
Background About 146,000 people were forced into long-term evacuation due to the nuclear power plant accident caused by the Great East Japan Earthquake in 2011. Disaster is known to induce hypertension in survivors for a certain period, but it is unclear whether prolonged disaster stress influences chronic kidney disease (CKD). We conducted an observational cohort study to elucidate the effects of evacuation stress on CKD incidence. Methods Participants were individuals living in communities near the Fukushima nuclear power plant, aged 40–74 years without CKD as of their 2011 general health checkup (non-evacuees: n = 9780, evacuees: n = 4712). We followed new-onset CKD [estimated glomerular filtration rate (eGFR)
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- 2017
10. Influence of Post-disaster Evacuation on Incidence of Metabolic Syndrome
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Tetsuya Ohira, Atsushi Takahashi, Shunichi Fukuhara, Shunichi Yamashita, Hitoshi Suzuki, Akira Ohtsuru, Shigeatsu Hashimoto, Shingo Fukuma, Hiroaki Satoh, Kotaro Ozasa, Gen Kobashi, Masafumi Abe, Kenji Kamiya, Hitoshi Ohto, Mitsuaki Hosoya, Seiji Yasumura, Masato Nagai, Akira Sakai, and Yukihiko Kawasaki
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Adult ,Male ,Waist ,030204 cardiovascular system & hematology ,Logistic regression ,Disasters ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Earthquakes ,Internal Medicine ,medicine ,Fukushima Nuclear Accident ,Humans ,030212 general & internal medicine ,Aged ,Metabolic Syndrome ,business.industry ,Incidence ,Incidence (epidemiology) ,Biochemistry (medical) ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Disaster ,Life style ,Original Article ,Female ,Medical emergency ,Metabolic syndrome ,Cardiology and Cardiovascular Medicine ,business ,Evacuation ,Body mass index ,Demography ,Cohort study - Abstract
Aim After the Great East Japan Earthquake, over 160,000 residents near the Fukushima Daiichi Nuclear Power Plant were forced to evacuate due to a nuclear accident. Health problems in these evacuees have since become major issues. We examined the association between evacuation and incidence of metabolic syndrome (METS) among residents in Fukushima. Methods We conducted a cohort study among residents aged 40-74 years without METS at the time of the disaster in Fukushima. Among 20,269 residents who met the inclusion criteria before the disaster, 8,547 residents (3,697 men and 4,850 women; follow-up proportion: 42.2%) remained available for follow-up examinations after the disaster by the end of March 2013. The main outcome was incidence of METS, defined by guidelines from the Japanese committee, using data from the Comprehensive Health Check before and after the disaster. We divided participants by evacuation status and compared outcomes between groups. Using a logistic regression model, we estimated the odds ratio for incidence of METS, adjusting for potential confounders, age, gender, waist circumference, exercise habit, and alcohol consumption. Results Incidence of METS was higher in evacuees (men 19.2%, women 6.6%) than in non-evacuees (men 11.0%, women 4.6%). Evacuees had higher body mass index, waist circumference, triglycerides, and fasting plasma glucose after the disaster than non-evacuees. We found a significant association between evacuation and incidence of METS (adjusted odds ratio 1.72, 95% confidence interval; 1.46-2.02). Conclusion This is the first study to demonstrate that evacuation after a disaster is associated with increased incidence of METS.
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- 2017
11. Brainstem Cerebellum-type Posterior Reversible Encephalopathy Syndrome
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Shigeatsu Hashimoto and Kazuya Honda
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posterior reversible encephalopathy syndrome ,Cerebellum ,Pathology ,medicine.medical_specialty ,business.industry ,Posterior reversible encephalopathy syndrome ,General Medicine ,medicine.disease ,PRES ,Pictures in Clinical Medicine ,medicine.anatomical_structure ,Internal Medicine ,medicine ,Brainstem ,business - Published
- 2020
12. Latent Autonomous Cortisol Secretion From Apparently Nonfunctioning Adrenal Tumor in Nonlateralized Hyperaldosteronism
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Tomikazu Fukuoka, Takuyuki Katabami, Tatsuya Kai, Takamasa Ichijo, Yoshihiro Ogawa, Shintaro Okamura, Yoshiro Chiba, Masakatsu Sone, Youichi Ohno, Masanobu Yamada, Mitsuhide Naruse, Isao Kurihara, Mika Tsuiki, Yoshiyu Takeda, Yuichiro Yoshikawa, Nobuya Inagaki, Norio Wada, Shoichiro Izawa, and Shigeatsu Hashimoto
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Cortisol secretion ,Male ,medicine.medical_specialty ,Hydrocortisone ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Adrenal Gland Neoplasms ,Context (language use) ,Biochemistry ,Plasma renin activity ,Statistics, Nonparametric ,Cohort Studies ,Endocrinology ,Primary aldosteronism ,Adrenocorticotropic Hormone ,Japan ,Internal medicine ,Diabetes mellitus ,Hyperaldosteronism ,medicine ,Prevalence ,Humans ,Aldosterone ,Retrospective Studies ,Proteinuria ,business.industry ,Biochemistry (medical) ,Middle Aged ,medicine.disease ,Prognosis ,Logistic Models ,Dexamethasone suppression test ,Female ,medicine.symptom ,business ,Tomography, X-Ray Computed - Abstract
Context Adrenal tumors (ATs), even those diagnosed as nonfunctioning, may cause metabolic disorders. Some primary aldosteronism (PA) patients with ATs are diagnosed with bilateral PA based on adrenal venous sampling (AVS), and their ATs are apparently nonfunctioning. Objective To clarify the influence of apparently nonfunctioning ATs, we compared hormone levels and clinical complications between bilateral PA cases with and without ATs. Design, setting, and participants After retrospectively assessing 2814 patients with PA in the multicenter Japan PA study, bilateral PA cases on AVS were divided into cases with and without ATs by computed tomography findings. Importantly, patients with cortisol levels >1.8 µg/dL after the 1-mg dexamethasone suppression test (DST) were excluded. Clinical characteristics and biochemical data were compared between them. The correlation between AT size and hormone levels was also analyzed. Main outcome measures Analyzed were 196 bilateral PA patients with ATs and 331 those without ATs. Although basal cortisol and aldosterone levels were similar between them, cortisol levels after the 1-mg DST and the prevalences of diabetes mellitus and proteinuria were significantly higher and ACTH levels and plasma renin activity were significantly lower in cases with ATs than in those without. After adjusting for patients’ backgrounds, cortisol levels after the 1-mg DST and plasma renin activity remained significantly different between them. Moreover, cortisol levels after the 1-mg DST and ACTH levels correlated with AT size. Conclusions Apparently nonfunctioning ATs in bilateral PA cases may cause latent autonomous cortisol secretion, inducing diabetes and proteinuria.
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- 2018
13. High Prevalence of Diabetes in Patients With Primary Aldosteronism (PA) Associated With Subclinical Hypercortisolism and Prediabetes More Prevalent in Bilateral Than Unilateral PA: A Large, Multicenter Cohort Study in Japan
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Shoichiro Izawa, Michio Otsuki, Yuichi Fujii, Kohei Kamemura, Yoshihiro Ogawa, Shozo Miyauchi, Takuyuki Katabami, Kenji Ashida, Toshihiko Yanase, Yuko Akehi, Takamasa Ichijo, Yuichi Matsuda, Masakatsu Sone, Shintaro Okamura, Hirotaka Shibata, Katsutoshi Takahashi, Junji Kawashima, Norio Wada, Yui Shibayama, Takanobu Yoshimoto, Megumi Fujita, Minemori Watanabe, Atsushi Ogo, Mika Tsuiki, Hiroki Kobayashi, Tatsuya Kai, Takashi Yoneda, Tomoko Suzuki, Shigeatsu Hashimoto, Hironobu Umakoshi, Ryoko Motonaga, Nobuya Inagaki, Hiroshi Itoh, Masanobu Yamada, Isao Kurihara, Tomikazu Fukuoka, Yoshiyu Takeda, Koichi Yamamoto, Mitsuhide Naruse, Takashi Kawamura, and Yuichiro Yoshikawa
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Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Population ,030209 endocrinology & metabolism ,Cohort Studies ,Diabetes Complications ,Prediabetic State ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Primary aldosteronism ,Japan ,Internal medicine ,Diabetes mellitus ,Hyperaldosteronism ,Internal Medicine ,medicine ,Diabetes Mellitus ,Prevalence ,Humans ,030212 general & internal medicine ,Prediabetes ,education ,Aldosterone ,Cushing Syndrome ,Subclinical infection ,Aged ,Retrospective Studies ,Advanced and Specialized Nursing ,Aged, 80 and over ,Glycated Hemoglobin ,education.field_of_study ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,chemistry ,Female ,Glycated hemoglobin ,business ,Cohort study - Abstract
OBJECTIVE To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. RESEARCH DESIGN AND METHODS The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA1c] ≥6.5% [≥48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia ( RESULTS Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30–69 years. Logistic regression or χ2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.
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- 2018
14. Evacuation is a risk factor for diabetes development among evacuees of the Great East Japan earthquake: A 4-year follow-up of the Fukushima Health Management Survey
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Akira Ohtsuru, Tetsuya Ohira, Kotaro Ozasa, Seiji Yasumura, Yukihiko Kawasaki, Hiroshi Takahashi, Hiroyuki Suzuki, Mitsuaki Hosoya, Hiroaki Shishido, G Kobashi, Yoshimitsu Hayashi, Hitoshi Ohto, Masafumi Abe, Akira Sakai, Yoshihiro Sugiura, Kenji Kamiya, Masato Nagai, Shigeatsu Hashimoto, Ai Takahashi, and Hiroaki Satoh
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Male ,History ,Fukushima Nuclear Accident ,Endocrinology, Diabetes and Metabolism ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Japan ,Environmental protection ,Risk Factors ,Diabetes mellitus ,Environmental health ,Internal Medicine ,medicine ,Diabetes Mellitus ,Earthquakes ,Prevalence ,Humans ,030212 general & internal medicine ,Aged ,Health management system ,Incidence ,Follow up studies ,General Medicine ,Risk factor (computing) ,Middle Aged ,medicine.disease ,Female ,Follow-Up Studies - Abstract
Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mardi 7 novembre 2017
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- 2017
15. Chronic kidney disease score for predicting postoperative masked renal insufficiency in patients with primary aldosteronism
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Akira Shimatsu, Takeshi Usui, Mitsuhide Naruse, Hiroshi Okuno, Mika Tsuiki, Shigeatsu Hashimoto, Tetsuya Tagami, Tomoko Suzuki, Hironobu Umakoshi, Atsushi Ogo, Kanako Tanase-Nakao, Ataru Okumura, Kazutaka Nanba, and Takuyuki Katabami
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Adult ,Male ,Research design ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Urology ,Renal function ,urologic and male genital diseases ,Logistic regression ,Severity of Illness Index ,Postoperative Complications ,Endocrinology ,Primary aldosteronism ,Internal medicine ,Hyperaldosteronism ,Severity of illness ,medicine ,Humans ,In patient ,Renal Insufficiency ,Renal Insufficiency, Chronic ,Aged ,Receiver operating characteristic ,business.industry ,Adrenalectomy ,Middle Aged ,Prognosis ,medicine.disease ,female genital diseases and pregnancy complications ,Surgery ,Research Design ,Female ,business ,Follow-Up Studies ,Glomerular Filtration Rate ,Kidney disease - Abstract
SummaryContext Chronic kidney disease (CKD) is sometimes unmasked after unilateral adrenalectomy in patients with primary aldosteronism (PA) without expectation. Objective Our study aim was to elucidate factors responsible for developing postoperative CKD and to provide a simple scoring system to predict postoperative CKD in PA. Design and Patients Forty-five patients with PA treated with unilateral adrenalectomy and followed for at least 1 month postsurgery were studied. Thirty-one patients with non-PA adrenal disease who underwent unilateral adrenalectomy were also studied as control. Patients with pre-operative estimated glomerular filtration rate (eGFR)
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- 2014
16. Evacuation and Risk of Hypertension After the Great East Japan Earthquake: The Fukushima Health Management Survey
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Tetsuya Ohira, Mitsuaki Hosoya, Seiji Yasumura, Hiroaki Satoh, Hitoshi Suzuki, Akira Sakai, Akira Ohtsuru, Yukihiko Kawasaki, Atsushi Takahashi, Kotaro Ozasa, Gen Kobashi, Shigeatsu Hashimoto, Kenji Kamiya, Shunichi Yamashita, Masafumi Abe, Hitoshi Ohto, Shinichi Suzuki, Hirooki Yabe, Masaharu Maeda, Shirou Matsui, Keiya Fujimori, Tetsuo Ishikawa, Tsuyoshi Watanabe, Satoru Suzuki, Toshihiko Fukushima, Sanae Midorikawa, Hiromi Shimura, Hirofumi Mashiko, Aya Goto, Kenneth Eric Nollet, Shinichi Niwa, Hideto Takahashi, and Yoshisada Shibata
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Adult ,Male ,Fukushima Nuclear Accident ,Injury control ,Poison control ,030204 cardiovascular system & hematology ,Risk Assessment ,Severity of Illness Index ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Emergency Shelter ,Japan ,law ,Nuclear power plant ,Internal Medicine ,Confidence Intervals ,Earthquakes ,Prevalence ,Rescue Work ,Medicine ,Humans ,030212 general & internal medicine ,Longitudinal Studies ,Socioeconomics ,Proportional Hazards Models ,Health management system ,business.industry ,Disease progression ,Blood Pressure Determination ,Middle Aged ,medicine.disease ,Health Surveys ,Survival Rate ,Fukushima daiichi ,Hypertension ,Multivariate Analysis ,Disease Progression ,Female ,Medical emergency ,business ,Risk assessment ,Stress, Psychological - Abstract
On March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. This study assessed the hypothesis that evacuation may have increased the risk of hypertension among residents in Fukushima. A longitudinal study examined data collected from 31 252 Japanese participants aged 40 to 74 years sourced from general health checkups conducted in 13 communities between 2008 and 2010. Follow-up examinations were conducted from 2011 through 2013. A total of 21 989 participants (follow-up proportion, 70.4%) received follow-up examinations. Mean blood pressure significantly increased in both evacuees and nonevacuees after the disaster, with greater changes in blood pressure among the former. The changes in systolic and diastolic blood pressure among the evacuees and nonevacuees were +5.8/3.4 versus +4.6/2.1 mm Hg ( P P P =0.33/ P P P =0.37) for women, respectively. For men, after adjustment for confounding variables, the hazard ratio slightly decreased to 1.20, but the association was essentially unchanged. Blood pressure increased among residents, especially evacuees, in the evacuation zone of Fukushima prefecture after the Great East Japan Earthquake. Evacuation may be associated with an increased risk of hypertension among men in the 2 years after the disaster.
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- 2016
17. Angiotensin II type 1 receptor blocker attenuates the activation of ERK and NADPH oxidase by mechanical strain in mesangial cells in the absence of angiotensin II
- Author
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Tsuyoshi Watanabe, Robin A. Felder, Junichi Yatabe, Hironobu Sanada, Shigeatsu Hashimoto, Minoru Yoneda, Pedro A. Jose, and Midori Yatabe
- Subjects
Male ,MAPK/ERK pathway ,medicine.medical_specialty ,Angiotensin receptor ,Cytochalasin D ,Hypertension, Renal ,Physiology ,Renal glomerulus ,Gene Expression ,Tetrazoles ,Receptor, Angiotensin, Type 1 ,Rats, Sprague-Dawley ,Internal medicine ,Paracrine Communication ,medicine ,Animals ,Vasoconstrictor Agents ,NADH, NADPH Oxidoreductases ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,Egtazic Acid ,Cells, Cultured ,Chelating Agents ,Nucleic Acid Synthesis Inhibitors ,NADPH oxidase ,Mesangial cell ,biology ,Chemistry ,Angiotensin II ,Imidazoles ,NADPH Oxidase 1 ,Articles ,Rats ,Autocrine Communication ,MicroRNAs ,Oxidative Stress ,Endocrinology ,Mesangial Cells ,biology.protein ,Stress, Mechanical ,Olmesartan ,Angiotensin II Type 1 Receptor Blockers ,medicine.drug - Abstract
It has been reported that mechanical strain activates extracellular signal-regulated protein kinases (ERK) without the involvement of angiotensin II (Ang II) in cardiomyocytes. We examined the effects of mechanical strain on ERK phosphorylation levels in the absence of Ang II using rat mesangial cells. The ratio of phosphorylated ERK (p-ERK) to total ERK expression was increased by cyclic mechanical strain in a time- and elongation strength-dependent manner. With olmesartan [Ang II type 1 receptor (AT1R) antagonist] pretreatment, p-ERK plateau levels decreased in a dose-dependent manner (EC50= 1.3 × 10−8M, maximal inhibition 50.6 ± 11.0% at 10−5M); a similar effect was observed with RNA interference against Ang II type 1A receptor (AT1AR) and Tempol, a superoxide dismutase mimetic. In addition to the inhibition of p-ERK levels, olmesartan blocked the increase in cell surface and phosphorylated p47phoxinduced by mechanical strain and also lowered the mRNA expression levels of NADPH oxidase subunits. These results demonstrate that mechanical strain stimulates AT1R to phosphorylate ERK in mesangial cells in the absence of Ang II. This mechanotransduction mechanism is involved in the oxidative stress caused by NADPH oxidase and is blocked by olmesartan. The inverse agonistic activity of this AT1R blocker may be useful for the prevention of mesangial proliferation and renal damage caused by mechanical strain/oxidative stress regardless of circulating or tissue Ang II levels.
- Published
- 2009
18. Effects of Decreased Renal Cortical Expression of G Protein-Coupled Receptor Kinase 4 and Angiotensin Type 1 Receptors in Rats
- Author
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Hironobu Sanada, Ines Armando, Shigeatsu Hashimoto, Xiaoyan Wang, Sanae Midorikawa, Tsuyoshi Watanabe, Robin A. Felder, Pedro A. Jose, Junichi Yatabe, and Peter M. Andrews
- Subjects
Male ,G-Protein-Coupled Receptor Kinase 4 ,medicine.medical_specialty ,Kidney Cortex ,Physiology ,Blood Pressure ,Rats, Inbred WKY ,Receptor, Angiotensin, Type 1 ,Article ,Natriuresis ,Rats, Inbred SHR ,Internal medicine ,Renin ,Renin–angiotensin system ,Internal Medicine ,medicine ,Animals ,RNA, Messenger ,Phosphorylation ,Receptor ,Kidney ,G protein-coupled receptor kinase ,Chemistry ,Angiotensin II ,Receptors, Dopamine D1 ,Sodium ,hemic and immune systems ,Oligonucleotides, Antisense ,respiratory system ,Rats ,Blood pressure ,Endocrinology ,medicine.anatomical_structure ,Dopamine receptor ,Potassium ,Cardiology and Cardiovascular Medicine - Abstract
Abnormalities in renal angiotensin type 1 receptor (AT1R), D1 dopamine receptor (D1R) and G protein–coupled receptor kinase 4 (GRK4) are present in polygenic hypertension. Selective renal reduction of AT1R expression by intrarenal cortical infusion of antisense oligodeoxynucleotides (As-Odns) in conscious, uni-nephrectomized, sodium-loaded rats decreases proteinuria, normalizes the glomerular sclerosis index (GSI), increases the sodium excretion (UNaV), and modestly increases blood pressure (BP) in spontaneously hypertensive rats (SHR) but not in normotensive Wistar-Kyoto rats (WKY). In contrast, selective renal reduction of GRK4 expression by infusion of GRK4 As-Odns increases UnaV, attenuates the increase in arterial BP with age, and modestly decreases protein excretion in SHR, but not in WKY. In this study, we report that intrarenal cortical infusion of both GRK4 and AT1R As-Odns decreased BP and increased UNaV in SHR; these effects were also noted in WKY to a lesser extent. Infusion of SHR with this combination of As-Odns resulted in a decrease in proteinuria and improvement of GSI similar to those by AT1R As-Odn only. In contrast to the increased circulating angiotensin II and aldosterone levels induced by AT1R As-Odn alone, the combination of As-Odns decreased both, contributing to greater natriuresis and amelioration of hypertension than by GRK4 or AT1R As-Odn only. Our results indicate an interaction between GRK4-regulated receptors and the renin-angiotensin system in the regulation of renal function and BP.
- Published
- 2008
19. Amelioration of Genetic Hypertension by Suppression of Renal G Protein–Coupled Receptor Kinase Type 4 Expression
- Author
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Tetsuo Katoh, Shigeatsu Hashimoto, Tsuyoshi Watanabe, Jing Xu, Robin A. Felder, Yingjin Luo, Hironobu Sanada, Junichi Yatabe, Xiaoyan Wang, Sanae Midorikawa, Pedro A. Jose, Chunyu Zeng, and Ines Armando
- Subjects
Male ,G-Protein-Coupled Receptor Kinase 4 ,medicine.medical_specialty ,Kidney Cortex ,Natriuresis ,Renal function ,Blood Pressure ,Protein Serine-Threonine Kinases ,Biology ,Kidney ,Rats, Inbred WKY ,Excretion ,Rats, Inbred SHR ,Internal medicine ,Serine ,Internal Medicine ,medicine ,Animals ,Tissue Distribution ,Phosphorylation ,Receptor ,Protein kinase A ,G protein-coupled receptor kinase ,Myocardium ,Receptors, Dopamine D1 ,Sodium ,Oligonucleotides, Antisense ,Immunohistochemistry ,Diuresis ,Rats ,Endocrinology ,Blood pressure ,medicine.anatomical_structure ,Dopamine receptor ,Hypertension - Abstract
Abnormalities in D 1 dopamine receptor function in the kidney are present in some types of human essential and rodent genetic hypertension. We hypothesize that increased activity of G protein–coupled receptor kinase type 4 (GRK4) causes the impaired renal D 1 receptor function in hypertension. We measured renal GRK4 and D 1 and serine-phosphorylated D 1 receptors and determined the effect of decreasing renal GRK4 protein by the chronic renal cortical interstitial infusion (4 weeks) of GRK4 antisense oligodeoxynucleotides (As-Odns) in conscious- uninephrectomized spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar–Kyoto (WKY) rats. Basal GRK4 expression and serine-phosphorylated D 1 receptors were &90% higher in SHRs than in WKY rats and were decreased to a greater extent in SHRs than in WKY rats with GRK4 As-Odns treatment. Basal renal D 1 receptor protein was similar in both rat strains. GRK4 As-Odns, but not scrambled oligodeoxynucleotides, increased sodium excretion and urine volume, attenuated the increase in arterial blood pressure with age, and decreased protein excretion in SHRs, effects that were not observed in WKY rats. These studies provide direct evidence of a crucial role of renal GRK4 in the D 1 receptor control of sodium excretion and blood pressure in genetic hypertension.
- Published
- 2006
20. Single-Nucleotide Polymorphisms for Diagnosis of Salt-Sensitive Hypertension
- Author
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Sanae Midorikawa, Midori Sasaki, Jason H. Moore, Tsuyoshi Watanabe, Shigeatsu Hashimoto, Junichi Yatabe, Robin A. Felder, Gilbert M. Eisner, Scott M. Williams, John C. Pezzullo, Hironobu Sanada, Marylyn D. Ritchie, and Pedro A. Jose
- Subjects
Male ,G-Protein-Coupled Receptor Kinase 4 ,medicine.medical_specialty ,Candidate gene ,Genotype ,Dopamine ,Clinical Biochemistry ,Blood Pressure ,Single-nucleotide polymorphism ,Protein Serine-Threonine Kinases ,Cohort Studies ,Asian People ,Japan ,Internal medicine ,Renin ,Renin–angiotensin system ,Genetic model ,medicine ,Humans ,Genetic Predisposition to Disease ,Prodrugs ,Sodium Chloride, Dietary ,Polymorphism, Genetic ,Models, Genetic ,Multifactor dimensionality reduction ,business.industry ,Receptors, Dopamine D1 ,Sodium ,Biochemistry (medical) ,Dopaminergic ,Biological Transport ,Middle Aged ,Diet ,Endocrinology ,Blood pressure ,Hypertension ,Female ,Natriuretic Agents ,business - Abstract
Background: Salt-sensitive (SS) hypertension affects >30 million Americans and is often associated with low plasma renin activity. We tested the diagnostic validity of several candidate genes for SS and low-renin hypertension.Methods: In Japanese patients with newly diagnosed, untreated hypertension (n = 184), we studied polymorphisms in 10 genes, including G protein–coupled receptor kinase type 4 (GRK4), some variations of which are associated with hypertension and impair D1 receptor (D1R)-inhibited renal sodium transport. We used the multifactor dimensionality reduction method to determine the genotype associated with salt sensitivity (≥10% increase in blood pressure with high sodium intake) or low renin. To determine whether the GRK4 genotype is associated with impaired D1R function, we tested the natriuretic effect of docarpamine, a dopamine prodrug, in normotensive individuals with or without GRK4 polymorphisms (n = 18).Results: A genetic model based on GRK4 R65L, GRK4 A142V, and GRK4 A486V was 94.4% predictive of SS hypertension, whereas the single-locus model with only GRK4 A142V was 78.4% predictive, and a 2-locus model of GRK4 A142V and CYP11B2 C-344T was 77.8% predictive of low-renin hypertension. Sodium excretion was inversely related to the number of GRK4 variants in hypertensive persons, and the natriuretic response to dopaminergic stimulation was impaired in normotensive persons having ≥3 GRK4 gene variants.Conclusions: GRK4 gene variants are associated with SS and low-renin hypertension. However, the genetic model predicting SS hypertension is different from the model for low renin, suggesting genetic differences in these 2 phenotypes. Like low-renin testing, screening for GRK4 variants may be a useful diagnostic adjunct for detection of SS hypertension.
- Published
- 2006
21. Differential Effects of Angiotensin II Type-1 Receptor Antisense Oligonucleotides on Renal Function in Spontaneously Hypertensive Rats
- Author
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Minoru Yoneda, Tsuyoshi Watanabe, Sanae Midorikawa, Tetsuo Katoh, Shigeatsu Hashimoto, Peter M. Andrews, Junichi Yatabe, Hironobu Sanada, Midori Sasaki, Robin A. Felder, and Pedro A. Jose
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Receptor expression ,Natriuresis ,Renal function ,Blood Pressure ,Kidney ,Rats, Inbred WKY ,Receptor, Angiotensin, Type 1 ,chemistry.chemical_compound ,Rats, Inbred SHR ,Internal medicine ,Renin ,Renin–angiotensin system ,Internal Medicine ,medicine ,Animals ,Aldosterone ,Angiotensin II receptor type 1 ,Histocytochemistry ,Angiotensin II ,Oligonucleotides, Antisense ,Diuresis ,Rats ,Proteinuria ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Mineralocorticoid ,Hypertension ,Potassium ,Angiotensin II Type 1 Receptor Blockers - Abstract
The effect of selectively decreasing renal angiotensin II type 1 (AT 1 ) receptor expression on renal function and blood pressure has not been determined. Therefore, we studied the consequences of selective renal inhibition of AT 1 receptor expression in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in vivo. Vehicle, AT 1 receptor antisense oligodeoxynucleotides (AS-ODN), or scrambled oligodeoxynucleotides were infused chronically into the cortex of the remaining kidney of conscious, uninephrectomized WKY and SHR on a 4% NaCl intake. Basal renal cortical membrane AT 1 receptor protein was greater in SHR than in WKY. In WKY and SHR, AS-ODN decreased renal but not cardiac AT 1 receptors. AT 1 receptor AS-ODN treatment increased plasma renin activity to a greater extent in WKY than in SHR. However, plasma angiotensin II and aldosterone were increased by AS-ODN to a similar degree in both rat strains. In SHR, sodium excretion was increased and sodium balance was decreased by AS-ODN but had only a transient ameliorating effect on blood pressure. Urinary protein and glomerular sclerosis were markedly reduced by AS-ODN–treated SHR. In WKY, AS-ODN had no effect on sodium excretion, blood pressure, or renal histology but also modestly decreased proteinuria. The major consequence of decreasing renal AT 1 receptor protein in the SHR is a decrease in proteinuria, probably as a result of the amelioration in glomerular pathology but independent of systemic blood pressure and circulating angiotensin II levels.
- Published
- 2005
22. Elevation of Serum Soluble E- and P-Selectin in Patients with Hypertension Is Reversed by Benidipine, a Long-Acting Calcium Channel Blocker
- Author
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Tetsuo Katoh, Shigeatsu Hashimoto, Junichi Yatabe, Hironobu Sanada, T. Baba, Midori Yatabe, Sanae Midorikawa, and Tsuyoshi Watanabe
- Subjects
Male ,Dihydropyridines ,medicine.medical_specialty ,Endothelium ,Physiology ,medicine.drug_class ,Blotting, Western ,Calcium channel blocker ,Essential hypertension ,chemistry.chemical_compound ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,business.industry ,Middle Aged ,Calcium Channel Blockers ,medicine.disease ,P-Selectin ,Endocrinology ,Blood pressure ,medicine.anatomical_structure ,chemistry ,Case-Control Studies ,Decreased blood pressure ,Hypertension ,Benidipine ,Female ,E-Selectin ,Cardiology and Cardiovascular Medicine ,business ,Cell Adhesion Molecules ,Selectin - Abstract
Hypertension is a major risk factor for atherosclerotic cardiovascular disease. Selectins, cell-surface adhesion molecules involved in leukocyte rolling and attachment to the vascular endothelium, play a role in the initiation of atherosclerosis. We investigated whether or not serum levels of soluble adhesion molecules are elevated in patients with essential hypertension (EH) and examined whether antihypertensive therapy lowers such levels. Twenty-one patients who had untreated mild to moderate EH without diabetes mellitus, hyperlipidemia, or obesity were recruited at a clinic for hypertensive patients. Blood pressure was measured, and the serum levels of soluble E-selectin, P-selectin, L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular-cell adhesion molecule 1 (VCAM-1) were determined by enzyme-linked immunosorbent assays before and after 12, 24, and 53 weeks of antihypertensive treatment with benidipine, a long-acting calcium channel blocker, given at a dose of 6 mg/day for 53 weeks. As a control, 21 age- and sex-matched patients without hypertension were studied. Serum E- and P-selectin levels were significantly higher in the subjects with EH than in the controls (p0.01). There were no differences in serum levels of soluble L-selectin, VCAM-1, or ICAM-1 levels between the patients with EH and the controls. Treatment with benidipine decreased the elevated blood pressure over a 53-week study period (mean blood pressure: 119.8 +/- 6.5 mmHg at baseline, 101.0 +/- 5.9 mmHg at 12 weeks, 98.6 +/- 7.3 mmHg at 24 weeks, and 93.9 +/- 5.5 mmHg at 53 weeks). Serum levels of soluble E- and P-selectin decreased after the initiation of benidipine treatment and correlated with diastolic blood pressure. Serum levels of soluble L-selectin, VCAM-1, and ICAM-1 did not change significantly during the period of benidipine treatment. Benidipine treatment reduced the content of P-selectin in the platelets from patients with EH, as determined by Western blot analysis. In conclusion, decreased blood pressure may reduce the rate of progression of atherosclerosis by affecting the expression of E- and P-selectin in the endothelium, the platelets, or both. Benidipine may be protective against vascular damage in people with hypertension, not only by lowering blood pressure, but also by inhibiting the expression of selectins.
- Published
- 2005
23. Inhibition of Growth Hormone Excess Reduces Insulin Resistance and Ovarian Dysfunction in a Lean Case of Polycystic Ovary Syndrome with a Growth-Hormone-Producing Pituitary Adenoma
- Author
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Hironobu Sanada, Sanae Midorikawa, Junichi Yatabe, Shigeatsu Hashimoto, and Tsuyoshi Watanabe
- Subjects
Adenoma ,Adult ,medicine.medical_specialty ,endocrine system diseases ,Somatotropic cell ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Dopamine Agents ,Pituitary Function Tests ,Endocrinology ,Insulin resistance ,Pituitary adenoma ,Internal medicine ,Humans ,Insulin ,Medicine ,Pituitary Neoplasms ,Acanthosis Nigricans ,Insulin-Like Growth Factor I ,Lisuride ,Bromocriptine ,Menstrual Cycle ,Glucose tolerance test ,medicine.diagnostic_test ,Human Growth Hormone ,business.industry ,Growth factor ,Ovary ,Theca Cell ,Glucose Tolerance Test ,medicine.disease ,Magnetic Resonance Imaging ,Polycystic ovary ,female genital diseases and pregnancy complications ,Pancreatic Function Tests ,Theca Cells ,Acromegaly ,Pediatrics, Perinatology and Child Health ,Female ,Insulin Resistance ,business ,Polycystic Ovary Syndrome - Abstract
A 23-year-old female with polycystic ovary syndrome (PCOS) and a growth-hormone (GH)-producing pituitary adenoma is described. A reduction in the elevated GH levels to normal levels following the administration of dopaminergic agents decreased plasma insulin-like growth factor (IGF)-1 and ovarian dysfunction. Menstrual cycles were therefore restored and the number of ovarian cysts reduced, suggesting that insulin and/or IGF-1, stimulators of theca cell proliferation, may be pathogenetic factors in PCOS.
- Published
- 2003
24. Effects of metformin on endocrine, metabolic milieus and endometrial expression of androgen receptor in patients with polycystic ovary syndrome
- Author
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Akiko Ito-Yamaguchi, Shigeatsu Hashimoto, Atsuko Kumagami, Ryota Suganuma, Keiya Fujimori, and Hiromi Yoshida-Komiya
- Subjects
Adult ,Blood Glucose ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,Endometrium ,Body Mass Index ,Young Adult ,Endocrinology ,Insulin resistance ,Internal medicine ,medicine ,Endocrine system ,Humans ,Hypoglycemic Agents ,Insulin ,Testosterone ,Prospective Studies ,Ovulation ,media_common ,business.industry ,nutritional and metabolic diseases ,Obstetrics and Gynecology ,Luteinizing Hormone ,medicine.disease ,Polycystic ovary ,Metformin ,Androgen receptor ,medicine.anatomical_structure ,Receptors, Androgen ,Female ,Follicle Stimulating Hormone ,Insulin Resistance ,business ,Luteinizing hormone ,medicine.drug ,Polycystic Ovary Syndrome - Abstract
To evaluate effects of metformin on endocrine, metabolic parameters and endometrial androgen receptor (AR) expression in polycystic ovary syndrome (PCOS).Prospective observational study.We analyzed blood samples from 10 PCOS patients, of whom endometrium was also analyzed in five patients. Before and after three months of metformin treatment, endocrine, glucose metabolic parameters and the endometrial AR expressions were assessed. The relative expression levels of AR were examined by immunohistochemistry.The group post-treatment mean of homeostasis model assessment insulin resistance (HOMA-IR) for all patients was significantly lower than the pretreatment. Ovulation was restored in five out of 10 patients. The group post-treatment means of luteinizing hormone (LH) and HOMA-IR for the five ovulatory patients were significantly lower. The relative expression levels of endometrial AR were decreased in four out of the five patients as compared with pretreatment. In the four patients, one or more of the parameters, HOMA-IR, LH or free testosterone, decreased compared with pretreatment.Metformin was effective in decreasing HOMA-IR, LH, free testosterone and the relative expression levels of AR. Furthermore, metformin might improve the systemic and local environment of the uterus caused by hyperandrogenemia in PCOS patients with insulin resistance.
- Published
- 2014
25. The improvement of insulin resistance in patients with adrenal incidentaloma by surgical resection
- Author
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Hironobu Sanada, Shigeatsu Hashimoto, Tsuyoshi Watanabe, Takayuki Suzuki, and Sanae Midorikawa
- Subjects
medicine.medical_specialty ,Glucose tolerance test ,medicine.diagnostic_test ,business.industry ,Endocrinology, Diabetes and Metabolism ,Incidentaloma ,Insulin ,medicine.medical_treatment ,Adrenalectomy ,medicine.disease ,Adrenocortical adenoma ,Impaired glucose tolerance ,Endocrinology ,Insulin resistance ,Blood pressure ,Internal medicine ,medicine ,business - Abstract
OBJECTIVE Several recent studies have indicated that patients with adrenal incidentaloma often have disturbed glucose tolerance or/and hypertension. It is unclear whether these metabolic conditions could be caused by adrenal incidentaloma. We investigated the prevalence of disturbed glucose tolerance, hypertension and insulin resistance in the patients with non-functioning adrenal incidentaloma and evaluated the changes of the parameters such as glucose tolerance, blood pressure and insulin sensitivity after adrenalectomy. PATIENTS AND METHODS Among 15 patients with incidentally discovered adrenal tumours in our department from 1996 to 1999, 4 patients were diagnosed as having pre-clinical Cushing's syndrome and the other 11 as having non-functioning tumours based on detailed endocrinological examinations including dexamethasone suppression testing. Four tumours with pre-clinical Cushing's syndrome and 8 tumours out of 11 patients with non-functioning tumours were diagnosed histopathologically as adrenocortical adenomas and the other 3 as of non-adrenal origin including a myelolipoma, an adrenal vascular cyst and an endothelioma. The prevalence of disturbed glucose tolerance was determined with an oral glucose tolerance test, and insulin sensitivity was evaluated by the method of steady state of plasma glucose (SSPG). RESULTS All 12 patients with adrenocortical adenoma exhibited insulin resistance based on the SSPG (6·9–13·2 mmol/l). Before surgical removal of the tumours, the SSPG titre was relatively higher in the patients with pre-clinical Cushing's syndrome than in those with non-functioning with adrenocortical adenoma (mean value 11·65 vs. 8·99 mmol/l), whereas 2 of the 3 patients with non-adrenocortical tumours did not have insulin resistance. Among the 12 patients with adrenocortical adenoma, 7 (58%) and 9 (75%) patients exhibited hypertension and disturbed glucose tolerance, respectively. After removal of the tumours, SSPG of the patients with adrenocortical adenoma, but not that of the other 3 patients with non-cortical tumours, was significantly decreased compared to pre-adrenalectomy values. There are no significant differences in the changes of SSPG titres between in pre-clinical Cushing's syndrome and in non-functioning adrenocortical adenoma. Systolic blood pressure, but not diastolic blood pressure, was also significantly decreased in the patients with adrenocortical adenoma. CONCLUSION High prevalences of disturbed glucose tolerance, insulin resistance and hypertension were found among the patients with non-functioning adrenocortical tumours. Adrenocortical adenoma may be one of the risk factors for insulin resistance that is believed to induce disturbed glucose tolerance and/or hypertension. Therefore, it is useful to evaluate insulin resistance for the patients with adrenal incidentalomas since results are likely to be helpful in deciding whether to remove the tumour by surgery.
- Published
- 2001
26. Analysis of Cortisol Secretion in Hormonally Inactive Adrenocortical Incidentalomas: Study of in vitro Steroid Secretion and Immunohistochemical Localization of Steroidogenic Enzymes
- Author
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Takashi Suzuki, Sanae Midorikawa, Shigeatsu Hashimoto, Hironobu Sanada, Hironobu Sasano, and Tsuyoshi Watanabe
- Subjects
Cortisol secretion ,medicine.medical_specialty ,Adrenal gland ,Endocrinology, Diabetes and Metabolism ,Incidentaloma ,Biology ,Corticotropin-releasing hormone ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,Dexamethasone suppression test ,medicine ,Secretion ,Dexamethasone ,Hormone ,medicine.drug - Abstract
Adrenal incidentalomas have recently increased in incidence, and thus it has become important to establish clinical management of these patients. It is also important to evaluate whether these tumors are different from preclinical or overt Cushing's syndrome in their steroidogenesis. In this study, we therefore examined steroidogenesis of hormonally inactive adrenal incidentalomas via short-term culture of tumor specimens, in addition to an immunohistochemical study of steroidogenic enzymes. Five patients (two men and three women) diagnosed with adrenocortical incidentaloma without any clinical signs of adrenocortical hormonal excess except for hypertension and disturbed glucose tolerance, were recruited for this study. Hormonal findings, including circadian rhythms for cortisol and ACTH secretion, the response of ACTH to CRH infusion and results of dexamethasone suppression test were all within normal limits in these patients. Immunoreactivity for all steroidogenic enzymes involved in cortisol production was detected in tumor cells in all cases examined. Results of in vitro steroidogenesis analysis using short-term culture revealed that levels of cortisol secretion varied among the cases. There were no differences in the immunolocalization of steroidogenic enzymes and/or the levels of cortisol secretion between these hormonally inactive tumors and preclinical and/or overt Cushing's syndrome. Dehydroepiandrosterone-sulfotransferase (DHEA-ST) immunoreactivity in nonneoplastic regions was suppressed in one case in which the tumor secreted cortisol similar to preclinical and/or overt Cushing's syndrome. These results demonstrate that the levels of in vitro steroid production and/or the immunolocalization of steroidogenic enzymes in hormonally inactive adrenocortical tumors vary markedly and are not overtly different from those of preclinical and/or overt Cushing's syndrome.
- Published
- 2001
27. The Role of β2-Adrenoceptor on the Pathogenesis of Insulin Resistance in Essential Hypertension
- Author
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Shigeatsu Hashimoto, Shuichi Shigetomi, Soitsu Fukuchi, Zen-o Yamada, Jinchi Kim, and Kiyonobu Tanaka
- Subjects
medicine.medical_specialty ,business.industry ,Mabuterol ,medicine.disease ,Essential hypertension ,Norepinephrine (medication) ,chemistry.chemical_compound ,Endocrinology ,Blood pressure ,Epinephrine ,Insulin resistance ,Basal (medicine) ,chemistry ,Internal medicine ,medicine ,Regular insulin ,business ,medicine.drug - Abstract
The role of beta 2-adrenoceptor on the pathogenesis of insulin resistance in essential hypertension (EH) was explored. After the measurement of blood pressure in 15 EH patients and 8 control subjects, EH patients were divided into two groups by the elevation of plasma NE (delta NE) 5 min after standing: 7 normoadrenergic EH (delta NE or = 140 pg/ml). On the morning after a 12-h overnight fast, regular insulin (0.1 U/kg) was injected intravenously, and glucose disappearance rate (GDR) was measured and used as an index of insulin sensitivity. On the following day, the test was reinvestigated following the administration of mabuterol, a beta 2 agonist. Plasma growth hormone (GH), cortisol, norepinephrine (NE) and epinephrine (Epi) were measured before and after the mabuterol administration. Although there were no significant differences of basal GDR among these three groups, mabuterol induced a considerable decrease in GDR in EH patients but not in control subjects. There was no significant difference in the decrease of GDR between normo- and hyperadrenergic EH. The decrease in GDR tended to correlate with the mean blood pressure at rest in EH but not in normal subjects. Plasma glucose and serum insulin in EH patients were increased more than in normal subjects. Plasma GH, cortisol and Epi were not elevated by mabuterol, but plasma NE increased in each group, significantly in hyperadrenergic EH. There was no correlationship between the increase in plasma NE and the decrease in GDR after mabuterol.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
28. Losartan, a specific angiotensin II receptor antagonist, increases angiotensin I and angiotensin II release from isolated rat hind legs: Evidence for locally regulated renin-angiotensin system in vascular tissue
- Author
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Makio Tani, Hironobu Sanada, Shigeatsu Hashimoto, Kenji Mizuno, Makoto Ohtsuki, Soitsu Fukuchi, Hidetsuna Watanabe, Susumu Niimura, and Hiroshi Haga
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Tetrazoles ,Angiotensin II receptor antagonist ,Hindlimb ,Nephrectomy ,Losartan ,Muscle, Smooth, Vascular ,General Biochemistry, Genetics and Molecular Biology ,Renin-Angiotensin System ,Angiotensin Receptor Antagonists ,Internal medicine ,Renin–angiotensin system ,medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Chemistry ,Angiotensin II ,Biphenyl Compounds ,Imidazoles ,General Medicine ,Rats ,Perfusion ,Biphenyl compound ,Endocrinology ,medicine.anatomical_structure ,cardiovascular system ,Blood Vessels ,Angiotensin I ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Blood vessel - Abstract
The effect of Losartan (10(-9) to 10(-6) M) on angiotensins I and II release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal and bilaterally nephrectomized rats. Losartan increased dramatically both angiotensins I (Ang I) and II (Ang II) release in a dose-dependent fashion; the maximal percent increment in Ang I and Ang II release evoked by Losartan (10(-6) M) was about +380% and +160%, respectively, in normal rat hind legs. In nephrectomized animals, Losartan elicited a marked increase in both peptides dose-dependently. There was a highly positive correlation between the released amounts of Ang I and that of Ang II altered by Losartan in either normal (r = 0.954) or nephrectomized rats (r = 0.923). These results not only confirm the existence of a functional renin-angiotensin system in vascular tissues, but also suggest that the system is regulated by locally generated Ang II.
- Published
- 1992
29. Multiple endocrine neoplasia type 1 in end-stage renal failure
- Author
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Mitsuo Takahashi, Y Sakuma, Shinichi Suzuki, Shigeatsu Hashimoto, Hodaka Suzuki, Seiichi Takenoshita, Tsuyoshi Watanabe, Koichi Asahi, Shinji Kosugi, and Tetsuo Katoh
- Subjects
Nephrology ,Parathyroidectomy ,Adult ,Male ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Urology ,Parathyroid hormone ,Parathyroid Glands ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,medicine ,Multiple Endocrine Neoplasia Type 1 ,Humans ,Multiple endocrine neoplasia ,Blood urea nitrogen ,Creatinine ,Hyperparathyroidism ,business.industry ,Middle Aged ,medicine.disease ,Pedigree ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Parathyroid Hormone ,Kidney Failure, Chronic ,Parathyroid gland ,Calcium ,Female ,business - Abstract
A 59-year-old woman with chronic renal failure due to type 2 diabetes mellitus (DM) is presented. Her father and a brother had a history of brain tumor. Her blood urea nitrogen and serum creatinine levels were 102 mg/dl and 4.5 mg/dl, respectively. Her serum Ca(2+) and Pi were within the normal range (9.4 mg/dl and 5.4 mg/dl, respectively). Her intact parathyroid hormone (PTH) level was 1 730 000 pg/ml. A (99m)Tc-methoxy-isobutylisonitrile scintigraphy showed high uptake in three parathyroid glands. A magnetic resonance image showed microadenoma in the pituitary gland. The serum gastrin level was high. Genetic examination revealed a mutation of the MEN1 gene (894-9 G --A). From these findings, she was diagnosed with multiple endocrine neoplasia (MEN) type 1. Subsequently, a parathyroidectomy was performed successfully, a parathyroid gland was transplanted to her right forearm, and her serum Ca(2+) level was controlled at 8.5-9.0 mg/dl. It is very important to identify MEN1 if an end-stage renal disease (ESRD) patient has hyperparathyroidism with multigland involvement. Examination of the MEN1 gene may be valuable to make an accurate diagnosis and choose the appropriate therapy in some ESRD patients with hyperparathyroidism.
- Published
- 2004
30. Improvement by Thiazolidinediones of Vascular Endothelial Cell Dysfunction in Diabetic Patients: A Possible New Physiological Role of PPARγ
- Author
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Shigeatsu Hashimoto, Sanae Midorikawa, Daishiro Yamada, Ken Kato, Tsuyoshi Watanabe, Hiroaki Satoh, Wakano Satoh, and Kazuhisa Tsukamoto
- Subjects
medicine.medical_specialty ,Bezafibrate ,business.industry ,Insulin ,medicine.medical_treatment ,Troglitazone ,Type 2 diabetes ,medicine.disease ,Tissue plasminogen activator ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Plasminogen activator inhibitor-1 ,medicine ,Endothelial dysfunction ,business ,Plasminogen activator ,medicine.drug - Abstract
This study was aimed to evaluate the significance and mechanism of vascular endothelial dysfunction in diabetic patients. Thirty-eight patients with type 2 diabetes mellitus were categorized to 3 groups according to the grade of retinopathy and treated for 4 weeks randomly with glibenclamide (n = 14) or troglitazone (n = 24). While plasma tissue plasminogen activator (tPA) (23.9 vs. 8.9 ng/ml; P< 0.05) and plasminogen activator inhibitor-1 (PAI-1) (23.6 vs. 11.8 pg/ml; P< 0.05) levels were significantly elevated in type 2 diabetes patients compared to the control subjects, the PAI-1 titer, but not tPA, was correlated with the severity of retinopathy. Four weeks-treatment by troglitazone was associated with significant reduction of PAI-1 level (20.1 from 26.8 pg/ml, P< 0.05), but not that of tPA, which was correlated with reduction of the steady state plasma glucose (SSPG) titer, but not with that of fasting plasma glucose. Immunoreactive PAI-1 or endothelin-1 (ET-1) were measured by ELISA in culture medium of human umbilical vein endothelial cells (HuVEC) or bovine vascular endothelial cells (bVEC), respectively, in the presence or absence of test agents (insulin, thiazolidinediones, 15-deoxy-delta 12, 14-prostaglandin J2 (15d-PGJ2), bezafibrate). Thiazolidinediones inhibited tumor necrosis factor α (TNF- α )-stimulated PAI-1 secretion and mRNA expression in a dosedependent fashion. Thiazolidinediones and 15d-PGJ2, but not bezafibrate, inhibited basal and insulin-stimulated ET-1 secretion and mRNA expression in a dose-dependent fashion.
- Published
- 2000
31. Differential regulation of blood pressure and renal function by renal at1 receptors in normotensive and spontaneously hypertensive rats
- Author
-
Minoru Yoneda, Tsuyoshi Watanabe, Junichi Yatabe, Sanae Midorikawa, Shigeatsu Hashimoto, Robin A. Felder, Hironobu Sanada, Midori Sasaki, and Pedro A. Jose
- Subjects
medicine.medical_specialty ,Angiotensin II receptor type 1 ,business.industry ,Urinary system ,Renal function ,medicine.disease ,Angiotensin II ,Blood pressure ,Endocrinology ,Internal medicine ,Renin–angiotensin system ,Internal Medicine ,Medicine ,Hypernatremia ,business ,Receptor - Published
- 2004
32. Direct evidence for erythropoietin-induced release of endothelin from peripheral vascular tissue
- Author
-
Koichi Asahi, Soitsu Fukuchi, Daishiro Yamada, Kenji Mizuno, Ken Katoh, Shigeatsu Hashimoto, Koichiro Okazaki, and Minoru Kuriki
- Subjects
Male ,medicine.medical_specialty ,Prostaglandin ,Vasodilation ,6-Ketoprostaglandin F1 alpha ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Erythropoietin ,Angiotensin II ,Endothelins ,General Medicine ,Endothelin 1 ,Recombinant Proteins ,Hindlimb ,Rats ,Thromboxane B2 ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Blood Vessels ,Angiotensin I ,Endothelin receptor ,Blood vessel ,medicine.drug - Abstract
The effect of recombinant human erythropoietin (r-HuEPO, 0.1 to 2.0 U/ml) on endothelin-1 (ET-1) release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal rats. r-HuEPO increased immunoreactive (ir-) ET-1 release in a dose-dependent fashion; the maximal percent increment in ir-ET-1 release evoked by r-HuEPO (2.0 U/ml) was about +210% over the basal rate of release. However, r-HuEPO showed no effect on release of angiotensin II, thromboxane B2 or vasodilatory prostaglandin I2 from the vasculature. These results not only provide direct evidence that r-HuEPO has the potential to specifically stimulate release of ET-1 from peripheral vascular beds, but, hence, suggest a contributory role of ET-1 in r-HuEPO-induced hypertension in anemic human subjects undergoing r-HuEPO therapy.
- Published
- 1994
33. Effects of losartan, a nonpeptide angiotensin II receptor antagonist, on cardiac hypertrophy and the tissue angiotensin II content in spontaneously hypertensive rats
- Author
-
Hironobu Sanada, Shigeatsu Hashimoto, Makio Tani, Susumu Niimura, Soitsu Fukuchi, Makoto Ohtsuki, Kenji Mizuno, and Hidetsuna Watanabe
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Heart Ventricles ,Radioimmunoassay ,Tetrazoles ,Angiotensin II receptor antagonist ,Blood Pressure ,Cardiomegaly ,Plasma renin activity ,General Biochemistry, Genetics and Molecular Biology ,Losartan ,Muscle hypertrophy ,Heart Rate ,Internal medicine ,Rats, Inbred SHR ,Renin–angiotensin system ,Renin ,medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Antihypertensive Agents ,Analysis of Variance ,business.industry ,Angiotensin II ,Biphenyl Compounds ,Body Weight ,Imidazoles ,General Medicine ,Organ Size ,Receptor antagonist ,Rats ,Endocrinology ,Blood pressure ,Hypertension ,cardiovascular system ,business ,hormones, hormone substitutes, and hormone antagonists ,circulatory and respiratory physiology ,medicine.drug - Abstract
Losartan, a recently developed nonpeptide angiotensin II (Ang II) receptor antagonist, was administered orally to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Cardiac weight and tissue Ang II, as well as plasma renin activity (PRA) and Ang II, were determined. Treatment with Losartan (10 mg/kg per day) lowered blood pressure markedly. Losartan reduced significantly the left ventricular weight by 11% compared with control rats. The left ventricular Ang II content was lowered by Losartan (18.6 +/- 0.9 pg/tissue; 21.9 +/- 0.9 pg/tissue, control, p less than 0.05), whereas PRA and plasma Ang II concentration were increased by the treatment. With the control and Losartan-treated animals, there was a significant positive correlation between the left ventricular weight and the tissue Ang II content (r = 0.563, p less than 0.05). These results provide evidence that cardiac tissue Ang II, rather than circulating Ang II, plays an important role in the pathophysiology of left ventricular hypertrophy of this animal model of human hypertension.
- Published
- 1992
34. Losartan prevents decline of cognitive function and decreases carotid intima-media thickness and pulse wave velocity along with reduction of blood pressure in elderly diabetic patients with hypertension
- Author
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Sanae Midorikawa, Ryo Muraoka, Minoru Yoneda, Shigeatsu Hashimoto, Hironobu Sanada, and Tsuyoshi Watanabe
- Subjects
medicine.medical_specialty ,Angiotensin receptor ,Angiotensin II receptor type 1 ,business.industry ,Arteriosclerosis ,medicine.disease ,Blood pressure ,Losartan ,Intima-media thickness ,Internal medicine ,cardiovascular system ,Internal Medicine ,medicine ,Cardiology ,cardiovascular diseases ,Systole ,business ,Pulse wave velocity ,hormones, hormone substitutes, and hormone antagonists ,circulatory and respiratory physiology ,medicine.drug - Abstract
P-402 Key Words: Losartan, Angiotensin Receptor (AT1) Antagonist, Cognitive Function, PWV
- Published
- 2004
35. E-selectin level may be a useful clinical marker for endothelial damage in hypertension
- Author
-
N. Imamura, Tsuyoshi Watanabe, Sanae Midorikawa, Akira Onozaki, Hironobu Sanada, and Shigeatsu Hashimoto
- Subjects
biology ,Endothelium ,P-selectin ,business.industry ,medicine.disease ,medicine.anatomical_structure ,Diabetes mellitus ,E-selectin ,Hyperlipidemia ,Immunology ,Internal Medicine ,biology.protein ,Medicine ,Immunohistochemistry ,L-selectin ,business ,Selectin - Published
- 2000
36. The Evidence for the Participation of Kinins in the Acute Antihypertensive Effect of Captopril in Hypertensive Patients
- Author
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Kenji Mizuno, Soitsu Fukuchi, Takahisa Toki, Junichiroh Matsui, Shigeatsu Hashimoto, Mitsuhiro Gotoh, and Kazumi Haruyama
- Subjects
medicine.medical_specialty ,Aldosterone ,business.industry ,Captopril ,medicine.disease ,Essential hypertension ,Hyperaldosteronism ,Plasma renin activity ,chemistry.chemical_compound ,Blood pressure ,Primary aldosteronism ,Mean blood pressure ,Endocrinology ,chemistry ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
In order to clarify the role of the kallikrein-kinin system in the hypotensive mechanisms of converting-enzyme inhibition, captopril was administered in a single oral dose of 50 mg to 17 hypertensive patients, of whom 14 had essential hypertension, one had chronic renal failure, one had primary aldosteronism, and one had glucocorticoid responsive hyperaldosteronism. Captopril lowered blood pressure remarkably in either low-renin or normal-, and high-renin hypertensives, however, there was no significant relationship between the fall in blood pressure and pretreatment levels of plasma renin activity (PRA) in any of the patients any time after the administration. PRA was significantly increased in normal- and high-renin hypertensives but not in low-renin patients. Plasma aldosterone concentration (PAC) was decreased significantly in normal- and high-renin patients, while no significant change in PAC was observed in patients with low-renin activity. Captopril elevated plasma bradykinin concentration (PBK) from a control value of 12.5 +/- 4.1 (mean +/- s.d.) to 20.3 +/- 7.7 pg/ml (p less than 0.001) at 30 min, and there was a significant correlation between changes in PBK and changes in mean blood pressure 120 min after the administration in all the patients (r = 0.741, p less than 0.01, n = 17). In one patient with primary aldosteronism, PBK increased from a baseline of 10.0 to a maximum value of 19.0 pg/ml, corresponding to the rapid fall in blood pressure. Also, in one patient with glucocorticoid responsive hyperaldosteronism, captopril increased PBK from a control of 14.1 to 27.9 pg/ml at 30 min, corresponding to the marked fall in blood pressure from 170/106 to 136/90 mmHg. From these findings, it is suggested that the accumulation of kinins following captopril administration plays a major role in the short-term reduction of blood pressure in hypertensive patients, especially in those with low renin-angiotensin activity.
- Published
- 1983
37. Increased the Activity of Sympathoadrenomedullary System and Decreased Renal Dopamine Receptor Contents after Short-term and Long-term Sodium Loading in Rats
- Author
-
Shuichi Shigetomi, Shuichi Ueno, Hideo Tosaki, Soitsu Fukuchi, Shigeatsu Hashimoto, and Hiroshi Kohno
- Subjects
Male ,medicine.medical_specialty ,Sympathetic Nervous System ,Epinephrine ,Sodium ,Urinary system ,chemistry.chemical_element ,Sodium Chloride ,Kidney ,High-performance liquid chromatography ,Receptors, Dopamine ,Norepinephrine (medication) ,Excretion ,Norepinephrine ,Internal medicine ,medicine ,Animals ,Receptor ,Rats, Inbred Strains ,Rats ,Dissociation constant ,Endocrinology ,chemistry ,Adrenal Medulla ,medicine.drug - Abstract
UNLABELLED We investigated the effects of short-term and long-term sodium loading on the sympathoadrenomedullary system and renal dopamine receptor. Male Wistar rats (n = 30) were raised drinking 1% NaCl for four weeks. Urinary norepinephrine and epinephrine excretion (UNE and UE) were measured before and 1, 2, 4 weeks after sodium loading by the use of high pressure liquid chromatography with fluorescence spectrophotometer. Renal plasma membranes were prepared by the ultracentrifugation method, and maximal binding capacity (Bmax) and dissociation constant (Kd) of renal dopamine receptor were determined by Scatchard analysis using 3-H-spiperone. RESULTS Sodium loading caused a slight but not significant decrease of free UNE after 1 and 2 weeks then clear increments of total (free + conjugated) UNE, free UE and total UE after 4 weeks. Bmax of renal dopamine receptor did not change after 1 and 2 weeks but significantly decreased after 4 weeks (before: 535.9 fmol/mg X protein, after 4 weeks: 327.2 fmol/mg X protein). Kd of renal dopamine receptor slightly elevated 1 week after sodium loading and then returned to the initial level. CONCLUSION These data suggest that short-term sodium loading may suppress the sympathetic activity, but long-term sodium loading may increase the activity of the sympathoadrenomedullary system with the decrease of renal dopamine receptor concentration. Increased catecholamines and decreased renal dopamine after long-term sodium loading may contribute to sodium-dependent hypertension.
- Published
- 1986
38. A Study on the Relation Between Dopamine Secretion and Salisensitivity in Essential Hypertension
- Author
-
Soitsu Fukuchi, Kenji Yaginuma, Shigeatsu Hashimoto, Masaaki Yamazaki, Shuichi Shigetomi, and Kazumi Haruyama
- Subjects
medicine.medical_specialty ,Aldosterone ,medicine.diagnostic_test ,Chemistry ,Sodium ,Furosemide ,chemistry.chemical_element ,Hematocrit ,Essential hypertension ,medicine.disease ,Plasma renin activity ,chemistry.chemical_compound ,Dopamine secretion ,Blood pressure ,Endocrinology ,Internal medicine ,medicine ,medicine.drug - Abstract
The study was designed to explore the mechanism of dopamine secretion related to blood pressure in patients with essential hypertension. The 19 patients with essential hypertension were administered to first 153 mEq of sodium and 70 mEq of potassium diet, next 51 mEq of sodium and finally 340 mEq of sodium for every one week. The patients whose mean blood pressure elevated 10 mmHg or more on the high-sodium loading and depleted 10 mmHg or more on the low-sodium loading were classified as A-, and depleted 10 mmHg or more on the high-sodium loading and elevated 10 mmHg or more on the low-sodium loading as B- and the other patients as C-group. The hypertensive patients were also classified to low- (below 1.0 ng/ml/h), normal- (from 1.0 to 6.0 ng/ml/h) and high- (above 6.0 ng/ml/h) renin groups from the results of plasma renin activity (PRA) obtained after an intravenous injection of furosemide (1 mg/kg) followed by 2-hour ambulation. PRA, plasma aldosterone concentration (PAC), plasma epinephrine concentration (PE), plasma norepinephrine concentration (PNE), plasma dopamine concentration (PDC), circulating plasma volume, body weight, hematocrit and pulse rate were measured at 8 a.m. after sodium loading for 8-days. The patients with essential hypertension were classified into 6 of A- and 2 of B- and 11 of C-groups with the maneuver of sodium loading. The A-group contained 5 patients with low-renin. The circulating plasma volume was relatively large (44.7 +/- 4.8 ml/kg) and markedly increased on the high-sodium loading in 6 patients of A-group. The increment of body weight was higher in A-group than the other groups on the high-sodium loading. In the 2 patients of B-group, hematocrit and pulse rate increased on the low-sodium and decreased on the high-sodium loading, and the variability were larger than the other groups. In the A-group, PRA was significantly low (0.5 +/- 0.4 ng/ml/h) and increased on the low-sodium loading and decreased on the high-sodium loading, and the variability of PRA was lesser than the other groups. In the A-group, PAC was within normal range (5.4 +/- 2.8 ng/dl) and the variation of PAC paralleled with the change of PRA, but the variability of PAC was remarkably low. PE and PNE were unchanged in the A- and the C-groups, but the significant high values were observed in the B-group on the high-sodium loading.
- Published
- 1983
39. A Case of Diabetes Mellitus with the Idiopathic Syndrome of Inappropriate Secretion of Antidiuretic Hormone
- Author
-
Shigeatsu Hashimoto, Kenji Yaginuma, Kenji Mizuno, Kazumi Haruyama, Soitsu Fukuchi, and Satsuki Ogawa
- Subjects
Male ,medicine.medical_specialty ,Inappropriate secretion ,business.industry ,Middle Aged ,medicine.disease ,Diabetes Complications ,Inappropriate ADH Syndrome ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Diabetes Mellitus ,medicine ,Humans ,Insulin ,business ,Antidiuretic ,Hormone - Published
- 1983
40. Evidence for the Existence of Inactive Renin in the Rat Brain
- Author
-
Makio Tani, Soitsu Fukuchi, Kenji Mizuno, Nobuyasu Kunii, Shigeatsu Hashimoto, Susumu Niimura, Ryuji Yabe, and Hiroaki Watari
- Subjects
Cerebellum ,medicine.medical_specialty ,Thalamus ,In Vitro Techniques ,Plasma renin activity ,Spontaneously hypertensive rat ,Rats, Inbred SHR ,Internal medicine ,Renin ,medicine ,Animals ,Trypsin ,Brain Chemistry ,Enzyme Precursors ,Chemistry ,Angiotensin II ,Rats ,Enzyme Activation ,Molecular Weight ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Cerebral cortex ,Hypothalamus ,Hypertension ,Medulla oblongata ,Kallikreins - Abstract
Inactive renin in the brain of spontaneously hypertensive rat was investigated. The results are as follows. Treatment with either trypsin or glandular kallikrein of the brain tissue extract caused a rapid and apparent increase in the renin activity at either 0 or 27 degrees C. The molecular weight of the active renin was estimated to be 41,000 or 50,000 daltons, while that of the trypsin-activatable inactive renin was found to be 44,000 or 57,000 daltons on a column chromatography with Sephadex G-100. The contents of the active renin was the highest in the hypothalamus, followed by the striatum, thalamus, midbrain, medulla oblongata, cerebral cortex and cerebellum, while the contents of the trypsin-activatable inactive renin was the highest in the hypothalamus, followed by the striatum, thalamus, cerebellum, midbrain, cerebral cortex and medulla oblongata. These results suggest that inactive renin(s) exist in the brain of spontaneously hypertensive rat. It seems likely that the brain renin-angiotensin system is modulated by the conversion of inactive to active renin(s), which, in turn, plays at least in part a role in the blood pressure regulation through generation of angiotensin II in spontaneously hypertensive rats.
- Published
- 1985
41. Direct evidence for local generation and release of angiotensin II in human vascular tissue
- Author
-
Soitsu Fukuchi, Kazuaki Shimamoto, Akira Satoh, Shigeatsu Hashimoto, Susumu Niimura, Makio Tani, Tadashi Inagami, and Kenji Mizuno
- Subjects
Umbilical Veins ,medicine.medical_specialty ,Angiotensins ,Captopril ,Biophysics ,In Vitro Techniques ,Peptide hormone ,Biochemistry ,Muscle, Smooth, Vascular ,Umbilical vein ,Pregnancy ,Internal medicine ,Renin–angiotensin system ,medicine ,Humans ,Molecular Biology ,Chromatography, High Pressure Liquid ,Vascular tissue ,biology ,Chemistry ,Angiotensin II ,Angiotensin-converting enzyme ,Cell Biology ,Kinetics ,Endocrinology ,biology.protein ,Female ,Angiotensin I ,Perfusion ,medicine.drug - Abstract
A direct measurement of both angiotensins I and II immunoreactive substances was made in the perfusate from isolated human umbilical vein perfused with Krebs-Ringer solution which was free of any component of the renin-angiotensin system. The identity of the immunoreactive peptides was confirmed as angiotensin I and angiotensin II by high-performance liquid chromatography in reference to standard compounds. The rate of release of angiotensins was 41.9 +/- 7.4 and 63.4 +/- 12.0 pg for angiotensins I and II, respectively, during the first perfusion period of 30 min, and it remained stable at least for 3 hours. Angiotensin-converting enzyme inhibitor captopril, added to the perfusion medium (10(-9) to 5 x 10(-6) M), suppressed immunoreactive angiotensin II release in a dose-dependent fashion; the maximal percent inhibition of angiotensin II release evoked by captopril (5 x 10(-6) M) was approximately 56%. These results taken together with the previous observations of presence of essential components of the renin-angiotensin system in vascular tissue provide direct evidence for local generation and subsequent release of angiotensin II in vascular beds of human beings.
- Published
- 1989
42. Effects of o, p′-DDD on Pituitary-gonadal Function in Patients with Cushing's Disease
- Author
-
Motoko Ojima, Masami Egawa, Nobuo Itoh, Yoshiro Kusano, Taihei Gomibuchi, Koji Satoh, Soitsu Fukuchi, and Shigeatsu Hashimoto
- Subjects
endocrine system ,medicine.medical_specialty ,business.industry ,medicine.drug_class ,Cholesterol side-chain cleavage enzyme ,Dehydroepiandrosterone ,Androgen ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Corticosterone ,Internal medicine ,medicine ,Pregnenolone ,Androstenedione ,business ,Corpus luteum ,hormones, hormone substitutes, and hormone antagonists ,Testosterone ,medicine.drug - Abstract
O,p'-DDD has a cytotoxic action and inhibits the cholesterol side chain cleavage enzyme, 11 beta-hydroxylase, 3 beta-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase and 21-hydroxylase of the adrenal cells. However, the effects of o,p'-DDD on gonadal steroidogenesis are still unknown. In the present study, the effects of o,p'-DDD on Plasma cortisol, pregnenolone, 17 alpha-hydroxypregnenolone (17-OH-pregnenolone), progesterone, 17 alpha-hydroxyprogesterone (17-OH-progesterone), 11-deoxycorticosterone (DOC), corticosterone, dehydroepiandrosterone (DHEA), delta 4-androstenedione (androstenedione), estradiol, and LH and FSH were investigated in 3 patients with Cushing's disease before and after the administration of o,p'-DDD. The results are presented here. In Case 1 (18 yr old female) who had had secondary amenorrhea for 2 years, the plasma levels of cortisol, pregnenolone, 17-OH-pregnenolone, DHEA, androstenedione, testosterone, estradiol and corticosterone were elevated. The basal levels of plasma LH and FSH and the responses of both gonadotropins were lower than those of women with eumenorrhea. The plasma levels of progesterone, DHEA and testosterone decreased to normal 2 months after the beginning of the administration of o,p'-DDD. She restored menstrual cycles ranging from 40 to 50 days 3 months after the administration of o,p'-DDD, but with anovulatory bleeding. She showed a biphasic body temperature pattern with plasma progesterone and estradiol levels indicating corpus luteum formation 11 months after the start of the treatment, when plasma cortisol as well as progesterone and androgen were reduced to normal. The basal levels of FSH and LH and responses of these gonadotropins were slightly improved at that time. The plasma levels of cortisol, DHEA and androstenedione were high in Case 2 (38 yr old male) and Case 3 (45 yr old male), whereas plasma testosterone level was normal in Case 2 and low in Case 3. The plasma levels of these 3 steroids were normalized 28 days after the beginning of the o,p'-DDD administration. These results suggest that o,p'-DDD does not interfere with gonadal steroidogenesis in Cushing's disease.
- Published
- 1988
43. A Case with 21-Hydroxylase Deficiency and Bartter's Syndrome Associated with a Ballanced 6-9 Translocation
- Author
-
Ryuji YABE, Kenji MIZUNO, Motoko OJIMA, Satsuki OGAWA, Shigeatsu HASHIMOTO, Nobuyasu KUNII, Kouichi KISHINO, Makio TANI, Susumu NIIMURA, Hiroaki WATARI, and Soitsu FUKUCHI
- Subjects
medicine.medical_specialty ,Adolescent ,Metabolic alkalosis ,Pigmentations ,Plasma renin activity ,Dexamethasone ,Translocation, Genetic ,Renin-Angiotensin System ,Excretion ,chemistry.chemical_compound ,Corticosterone ,Internal medicine ,Hyperaldosteronism ,medicine ,Humans ,Progesterone ,Chromosomes, Human, 6-12 and X ,Aldosterone ,Adrenal Hyperplasia, Congenital ,Chemistry ,Bartter Syndrome ,medicine.disease ,Angiotensin II ,Endocrinology ,Steroid Hydroxylases ,Female ,medicine.drug - Abstract
A 17-year-old female weighing 37 kg and 140 cm in height was referred to our hospital for evaluation of dwarfism and primary amenorrhea. She was delivered with 3350 g in weight and 50 cm in height after a ten month pregnancy without complications. No abnormal findings were revealed in physical appearance except critomegaly. Episodes of nausea, vomiting and dehydration were rare throughout her childhood, but she had a tendency to salt craving. At the age of 14, her height was 140 cm. On admission, her physical development was markedly retarded for her age, except external genitalia. Diffuse pigmentations on the trunk and extremities were observed. Her blood pressure was normal (112/62 mm Hg). Serum potassium concentration was 2.9 mEq/L. Arterial-blood gas analysis revealed metabolic alkalosis. Both of renin activity (PRA) and aldosterone concentration (PAC) in plasma at rest were markedly elevated to 15.5 ng/ml/h and 107.1 ng/dl, respectively. The plasma concentrations of pregnenolone (1449 ng/dl), progesterone (178 ng/dl), 17-OH-pregnenolone (1613 ng/dl), 17-OH-progesterone (180 ng/dl), dehydroepiandrosterone (3706 ng/dl), androstendione (824.6 ng/dl) and testosterone (900 ng/dl) were high, whereas deoxycorticosterone (15.7 ng/dl), corticosterone (0.65 microgram/dl) and cortisol (6.8 micrograms/dl) were within normal limits. Urinary 17-KS excretion showed high levels between 65.7 and 109.4 mg/day, while urinary 17-OHCS excretion was normal (5.7-7.0 mg/day). Vascular response to angiotensin II (A-II) was attenuated. Distal fractional chloride reabsorption was decreased (CH2O/CH2O+CCl = 0.62, normal: 0.92 +/- 0.04). Moderate hyperplasia of the juxtaglomerular cells was demonstrated in biopsy specimen of the kidney. Cytogenetic studies showed a 46, XX chromosome constitution with translocation of the long arm of chromosome 6 to the short arm of chromosome 9. Her mother as well as younger brother and sister, whose electrolytes and arterial-blood gas analysis showed normal values, had chromosomes with the same translocation. Treatment with dexamethasone (2 mg/day) reduced every adrenal steroids to normal range, but PRA and PAC remained high levels. Furthermore, neither hypokalemic alkalosis nor vasoreactivity to exogenous A-II was improved. Indomethacin (75 mg/day) decreased urinary excretion of prostaglandin E2 from a high level of 738.4 ng/day to 433.4 ng/day and normalized metabolic alkalosis. Vascular response to A-II was moderately improved. However, serum potassium remained low.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 1986
44. Multiple forms of immunoreactive renin in human adrenocortical tumour tissue from patients with primary aldosteronism
- Author
-
Nobuyasu Kunii, Hiroaki Watari, Tadashi Inagami, Susumu Niimura, Shigeatsu Hashimoto, Soitsu Fukuchi, Motoko Ojima, Kenji Mizuno, Makio Tani, and Ryuji Yabe
- Subjects
Adult ,Male ,Proteases ,medicine.medical_specialty ,Chromatography, Affinity ,Primary aldosteronism ,Internal medicine ,Hyperaldosteronism ,Renin ,Renin–angiotensin system ,medicine ,Humans ,Cathepsin ,biology ,Adrenal gland ,Adrenal cortex ,General Medicine ,Hydrogen-Ion Concentration ,Middle Aged ,medicine.disease ,Adrenal Cortex Neoplasms ,Isoenzymes ,Molecular Weight ,medicine.anatomical_structure ,Endocrinology ,Zona glomerulosa ,Concanavalin A ,Chromatography, Gel ,biology.protein ,Female ,Isoelectric Focusing - Abstract
1. There is increasing evidence which suggests that the adrenal gland contains the renin–angiotensin cycle. The localization of renin has been reported to be mainly in the zona glomerulosa rather than the fasciculata medullary portion. In the present study we have investigated extracts from aldosteronomas (n = 3), which are believed to derive from the zona glomerulosa cells. In addition, we have attempted to characterize the biochemical properties of the adrenal renin. 2. Sizable quantities of renin-like activity (32.0 ± 7.7 ng of angiotensin I generated h−1 mg−1 of protein, mean ± SEM) were detected in the extracts. This renin-like activity was inhibited by anti-renin antibody raised against pure renin (mean, 95% of the total renin-like activity), indicating that it was not due to the non-specific action of proteases such as cathepsin D. 3. The optimum pH of the tissue renin-like enzyme was 6.0 for rat plasma substrate. Differences were found, however, in the molecular mass (36000, 37000, 44000 and 48000), binding to concanavalin A and isoelectric points (4.40, 4.68 and 5.00). 4. These results confirm the existence of specific renin in aldosteronoma. Renin microheterogeneity could be evidence for local production of the enzyme.
- Published
- 1987
45. The Acute Effects of the New Angiotensin I-Converting Enzyme Inhibitor, Enalapril Maleate, on Blood Pressure, Plasma Renin, Aldosterone and Kinins in Hypertensive Patients
- Author
-
Kenji Mizuno, Mitsuhiro Gotoh, Nobuyasu Kunii, Shigeatsu Hashimoto, and Soitsu Fukuchi
- Subjects
medicine.medical_specialty ,Aldosterone ,business.industry ,medicine.disease ,Essential hypertension ,Plasma renin activity ,Renovascular hypertension ,chemistry.chemical_compound ,Mean blood pressure ,Blood pressure ,Endocrinology ,chemistry ,Enalapril Maleate ,Internal medicine ,Renin–angiotensin system ,Medicine ,business - Abstract
The acute antihypertensive effect of a new long-acting oral angiotensin I-converting enzyme (ACE) inhibitor, enalapril maleate, was assessed in 20 hypertensive patients, of whom 14 had essential hypertension, 4 had renovascular hypertension, one had hypertension associated with chronic renal failure, and one had primary aldosteronism. Enalapril maleate significantly lowered the blood pressure in either low-renin or normal- and high-renin hypertensives. There was a significant correlation for all patients as a group between the pretreatment levels of serum ACE activity and the reduction in mean blood pressure (r = -0.454, p less than 0.05, n = 20) 2 h after drug administration. The serum ACE activity decreased maximally 3 to 4 hours after drug administration and did not return to baseline levels within 24 h. There was a significant correlation between the reduction in mean blood pressure and changes in ACE activity 90 min and 2 h after drug administration, respectively, for all patients as a group (r = 0.495, p less than 0.05, n = 20, at 90 min; r = 0.508, p less than 0.05, n = 20, at 2 h). The plasma renin activity (PRA) significantly increased in normal- and high-renin hypertensives but not in low-renin hypertensives. There was a close correlation between the reduction in mean blood pressure and the PRA 8 h after drug administration in normal- and high-renin patients (r = -0.623, p less than 0.05, n = 13), while no such relationship was observed in low-renin patients. The plasma aldosterone concentration (PAC) significantly decreased within 3 h, the lowest values occurring at 8 h after drug administration, and it returned to baseline levels within 24 h in all patients. No relationship was found between the reduction in mean blood pressure and changes in PAC after drug administration in either low-renin or normal- and high-renin hypertensives. The plasma bradykinin concentration (PBC) increased within 1 h, the highest values occurring at 3 h after drug administration, and returned to baseline levels within 24 h in low-renin hypertensives, while the PBC was significantly increased at 4 h and had not returned to baseline levels within 24 h in normal- and high-renin hypertensives. There was a significant correlation between percentage changes in mean blood pressure and those in PBC 90 min after drug administration in normal- and high-renin hypertensives (r = -0.556, p less than 0.05, n = 13), while no relationship was observed between them in low-renin hypertensives.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 1985
46. Immunoreactive renin in human brain: Distribution and properties
- Author
-
Nobuyasu Kunii, Makio Tani, Kenji Mizuno, Hiroaki Watari, Susumu Niimura, Shigeatsu Hashimoto, Motoko Ojima, and Soitsu Fukuchi
- Subjects
medicine.medical_specialty ,Physiology ,Central nervous system ,Peptidyl-Dipeptidase A ,Biology ,Plasma renin activity ,Neuroblastoma ,Pineal gland ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Humans ,Cathepsin ,Kidney ,Brain Neoplasms ,Brain ,Human brain ,Molecular Weight ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Hypothalamus ,Child, Preschool ,Pituitary Gland ,Hypertension ,Female ,Isoelectric Focusing ,Cardiology and Cardiovascular Medicine - Abstract
Readily detectable levels of renin activity were demonstrated in the human brain. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases such as cathepsin D. The pineal gland was found to be the richest source of renin followed by the pituitary, hypothalamus and hippocampus. The substantia nigra, caudate nucleus, putamen and thalamus contained moderately high concentrations of renin. The brain renins from pineal and pituitary glands shared some biochemical features with well-known kidney renin, such as molecular weight (46, 000 daltons for pineal renin ; 37, 000-45, 000 daltons for pituitary renin), optimum pH (6.0-7.0), the presence of trypsin-activatable inactive renin, and a glycoprotein nature. However, the electro-focusing pattern of renin from pituitary tissue (pI = 4.43, 5.77) differed from that of plasma and kidney enzymes heretofore reported, a discrepancy which could be interpreted as evidence for the endogeneous synthesis of renin in the brain tissue. Furthermore, a high activity of immunoreactive renin was found in human neuroblastoma tissue. The biochemical characteristics of the neuroblastomal renin were generally similar to the known properties of kidney renin in many respects, providing evidence of the presence of the renin-angiotensin system within human neuronal cells.
- Published
- 1985
47. Effects of metoclopramide, a dopamine antagonist, on secretion of aldosterone and renin release in patients with primary aldosteronism
- Author
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Kenji Mizuno, Kenji Yaginuma, Masaaki Yamazaki, Shigeatsu Hashimoto, Soitsu Fukuchi, and Kaoru Ikeda
- Subjects
Adult ,Male ,medicine.medical_specialty ,Metoclopramide ,Hydrocortisone ,Plasma renin activity ,Dexamethasone ,chemistry.chemical_compound ,Primary aldosteronism ,Adrenocorticotropic Hormone ,Dopamine ,Internal medicine ,Renin–angiotensin system ,Hyperaldosteronism ,Renin ,medicine ,Humans ,Aldosterone ,business.industry ,Sodium ,Dopamine antagonist ,Middle Aged ,medicine.disease ,Prolactin ,Endocrinology ,chemistry ,Potassium ,Female ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
To assess the interaction between dopamine and aldosterone secretion in primary aldosteronism, the dopamine antagonist, metoclopramide (methoxy-2-chloro-5-procainamide), was given as an i.v. bolus (10 mg) to 5 patients with primary aldosteronism and 5 normal subjects treated with dexamethasone (2 mg/day) to eliminate an influence of ACTH. Metoclopramide increased plasma aldosterone concentration (PAC) in primary aldosteronism from 39.1 +/- 15.5 to 42.5 +/- 15.9 ng/100 ml (p less than 0.05) and also from 12.9 +/- 2.3 to 23.6 +/- 3.4 ng/100 ml (p less than 0.01) in normal subjects at 15 min. Plasma renin activity (PRA), and plasma concentrations of cortisol, potassium, and sodium did not significantly change with metoclopramide in either primary aldosteronism or normal subjects. Plasma prolactin increased by 12- and 20-fold in primary aldosteronism and in normal subjects, respectively, but there was no significant positive correlation between changes in PAC and in plasma prolactin in either primary aldosteronism or normal subjects. It is suggested that dopamine inhibits the secretion of aldosterone in primary aldosteronism as well as in normal subjects. It seems unlikely that dopamine affects the release of renin in primary aldosteronism.
- Published
- 1983
48. [Biochemical properties of renin in human pituitary tissue]
- Author
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Shigeatsu Hashimoto, Soitsu Fukuchi, Mitsuhiro Gotoh, Kenji Mizuno, and Motoko Ojima
- Subjects
Cathepsin ,medicine.medical_specialty ,Isoelectric focusing ,Chemistry ,Trypsin ,Plasma renin activity ,Chromatography, Affinity ,Molecular Weight ,Endocrinology ,Isoelectric point ,Affinity chromatography ,Sephadex ,Internal medicine ,Pituitary Gland ,Renin–angiotensin system ,Renin ,medicine ,Humans ,Isoelectric Point ,medicine.drug ,Glycoproteins - Abstract
The biochemical properties of renin, extracted from human pituitary specimens obtained at autopsy, were studied using a specific antirenin antibody raised against human kidney renin. The following results were obtained. The molecular weight of pituitary renin was estimated to be about 37,000 daltons by gel filtration through Sephadex G-100. The optimum pH of pituitary renin was between 6.0 approximately 7.0, while that of a renin-like substance which did not react with the antirenin antibody had an acidic pH of 4.0, with a pH comparable to that of the cathepsin D-like enzyme in the pituitary tissue. The presence of two different isoelectric-point species of pituitary renin was revealed by isoelectric focusing, one with a point of pH 4.47 and the other with that of pH 5.77. The Km value of pituitary renin was 37.9 microM for synthetic human renin substrate. Affinity chromatography of the pituitary renin on a Concanavalin-Sepharose column showed that most (87.4%) of the pituitary renin did not contain glycoprotein residues. Treatment with either trypsin or glandular kallikrein increased the renin activity, indicating the presence of an inactive form of renin in the pituitary tissue. From these findings, it is concluded that specific renin exists in human pituitary tissue. It seems likely that the pituitary renin is of local origin rather than contamination of the circulating enzyme.
- Published
- 1985
49. [Role of renal dopamine receptor in the pathogenesis of hypertension after sodium loading]
- Author
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Shuichi Ueno, Soitsu Fukuchi, Hiroshi Kohno, Shuichi Shigetomi, Kazuto Suenaga, Shigeatsu Hashimoto, and Hideo Tosaki
- Subjects
Male ,medicine.medical_specialty ,Metoclopramide ,Sodium ,Dopamine ,chemistry.chemical_element ,Kidney ,Receptors, Dopamine ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Receptor ,Aldosterone ,Radioimmunoassay ,Rats, Inbred Strains ,Prolactin ,Rats ,Dissociation constant ,Blood pressure ,Endocrinology ,chemistry ,Hypertension ,medicine.drug - Abstract
UNLABELLED The purpose of this study is to clarify the role of renal dopamine receptor in the pathogenesis of salt-dependent hypertension. Male Wistar rats were raised under three different conditions, control, 1% NaCl loading (NaCl) and 1% NaCl plus metoclopramide with a dose of 1.5 mg/kg daily (MC), for 2 weeks. Then, renal plasma membranes were prepared by ultracentrifugation method, and maximal binding capacity (Bmax) and dissociation constant (Kd) were determined by Scatchard analysis using 3H-spiperone. And plasma aldosterone and prolactin concentration in these three groups were measured by radioimmunoassay. RESULTS Systolic blood pressure measured tail-cuff method significantly elevated in MC group, but not control and NaCl group. Bmax of renal dopamine receptor was 535.9 +/- 85.0 fmol/mg protein, 594.9 +/- 159.3 fmol/mg protein, 529.1 +/- 166.1 fmol/mg protein, in control, NaCl and MC group, respectively. Kd of renal dopamine receptor in NaCl group was significantly lower than control (p less than 0.05). Renal dopamine contents of NaCl and MC group were lower than control. There was a negative correlation between renal dopamine content and Bmax of renal dopamine receptor in NaCl group (r = -0.95, p less than 0.02). In MC group, plasma aldosterone concentration was slightly higher than control and NaCl group, but there was no differences in plasma prolactin concentration among these three groups.
- Published
- 1986
50. Biochemical evidence for existence of immunoreactive renin in human prolactinoma tissue
- Author
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Susumu Niimura, Kenji Mizuno, Soitsu Fukuchi, Nobuyasu Kunii, Yoshio Kusano, Hiroaki Watari, Motoko Ojima, Makio Tani, Shigeatsu Hashimoto, and Ryuji Yabe
- Subjects
Proteases ,medicine.medical_specialty ,Pituitary gland ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Chromatography, Affinity ,Internal medicine ,Renin–angiotensin system ,Renin ,medicine ,Humans ,Pituitary Neoplasms ,Isoelectric Point ,General Pharmacology, Toxicology and Pharmaceutics ,Prolactinoma ,chemistry.chemical_classification ,Kidney ,Molecular mass ,General Medicine ,medicine.disease ,Prolactin ,Molecular Weight ,Enzyme ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Chromatography, Gel ,Specific activity - Abstract
High activity of renin was demonstrated in human prolactinoma tissue. This activity was almost completely inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 5.04 ng of angiotensin I generated/mg of protein per h, comparable to that of the pituitary tissue prepared from postmortem human subjects. The biochemical properties of the prolactinoma renin were generally similar to those of well-known kidney enzyme, such as molecular mass (Mr=46, 000), optimum pH (6.0), and glycoprotein nature. However, the isoelectric points (pI) of the prolactinoma renin pI=4.90, 5.04, 5.24 and 5.41) differed somewhat from those of plasma and kidney renins reported hitherto. These results indicate that true renin can be produced in human prolactinoma tissue.
- Published
- 1986
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