著者
Kei Segawa Miki Watanabe-Matsui Toshitaka Matsui Kazuhiko Igarashi Kazutaka Murayama
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.247, no.3, pp.153-159, 2019 (Released:2019-03-09)
参考文献数
30
被引用文献数
8

Heme is one of the key factors involved in the oxidative stress response of cells. The transcriptional repressor Bach1 plays an important role in this response through its heme-binding activity. Heme inhibits the transcriptional-repressor activity of Bach1, and can occur in two binding modes: 5- and 6-coordinated binding. The Cys-Pro (CP) motif has been determined to be the heme-binding motif of Bach family proteins. The sequence of Bach1 includes six CP motifs, and four CP motifs are functional. With the aim of elucidating the molecular mechanism of heme-Bach1 regulation, we conducted biophysical analyses focusing on the C-terminal region of mouse Bach1 (residues 631-739) which is located after the bZip domain and includes one functional CP motif. UV-Vis spectroscopy indicated that the CP motif binds heme via 5-coordinated bond. A mutant, which included a cysteine to alanine substitution at the CP motif, did not show 5-coordination, suggesting that this binding mode is specific to the CP motif. Surface plasmon resonance revealed that the binding affinity and stoichiometry of heme with the Bach1 C-terminal region were KD = 1.37 × 10–5 M and 2.3, respectively. The circular dichroism spectrum in the near-UV region exhibited peaks for heme binding to the CP motif. No significant spectral shifts were observed in the far-UV region when samples with and without heme were compared. Therefore, disordered-ordered transition such as “coupled folding and binding” is not involved in the Bach1-heme system. Consequently, the heme response of this C-terminal region is accomplished by disorder-disorder conformational alteration.
著者
Jin Qi Yaoqi Yang Ping Hao Jianqiang Xu
出版者
東北ジャーナル刊行会
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.242, no.4, pp.335-335, 2017 (Released:2017-09-06)

We reported “Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression” in Tohoku J. Exp. Med., 2017, 241 (1), 55-63; doi: 10.1620/tjem.241.55. After publication of the paper, we have become aware of the ethical violation in collecting the samples from some patients. We therefore wish to retract the paper and apologize for any inconvenience caused by the retraction.
著者
Wenwen Pang Pengcheng Shang Qingfeng Li Jiao Xu Lei Bi Jing Zhong Xiaofang Pei
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.244, no.3, pp.231-242, 2018 (Released:2018-03-20)
参考文献数
38
被引用文献数
30

Opportunistic infections (OIs) are the most significant complication of human immunodeficiency virus (HIV) infection. The prevalence of OIs differs among various countries in part due to different climates and socio-economic conditions. We, therefore, carried out the retrospective study at the Public Health Clinical Center of Chengdu, Sichuan to comprehensively investigate the prevalence of OIs, predictors of OIs, and risk factors for in-hospital death among HIV-infected patients. Sichuan in West China is characterized by the largest population living with HIV/Acquired immunodeficiency syndrome (AIDS) across China. In total, we reviewed 954 cases of HIV infection, admitted to the hospital during January 2014 to December 2015, and found that bacterial pneumonia (25.8%) was the most common OIs, followed by candida infection (18.3%), Pneumocystis jiroveci pneumonia (11.9%), tuberculosis (11.5%), infectious diarrhoea (9.3%), cryptococcus infection (7.3%), cytomegalovirus infection (4.9%), toxoplasmosis (4.6%), hepatitis C (4.0%), nontuberculous mycobacteria desease (2.2%) and Penicillium marneffei infection (0.3%). We also found two strongest risk factors for in-hospital mortality: CD4+T cell counts of less than 100 cells/μL and not receiving antiretroviral therapy. Moreover, the study revealed the specific pathogens causing bacterial pneumonia and/or candida infection, the effect of tuberculosis on CD4+T cell counts, and the drug resistance of Mycobacterium tuberculosis among HIV-infected and non-HIV-infected patients. The present findings may aid in the clinical diagnosis and treatment of HIV-infected patients, and could help developing efficient public health strategies in China.
著者
Yusuke Matsuyama Toru Tsuboya Shun-ichiro Bessho Jun Aida Ken Osaka
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.244, no.2, pp.163-173, 2018 (Released:2018-03-01)
参考文献数
29
被引用文献数
12

Healthcare utilization after natural disasters remains understudied. In general, people in Japan pay 10%-30% of total amount of costs, according to their health insurance plan. A policy exempting survivors from copayments was introduced after the Great East Japan Earthquake in March 2011, which had a magnitude of 9.0 on the Richter scale and followed by devastating tsunamis. Among the disaster-affected areas, Miyagi prefecture experienced the largest number of deaths and the greatest extent of damage. However, the exemption was suspended in Miyagi prefecture from April, 2013, because of the huge governmental financial burden due to the immensity of damage from the disaster. Subsequently, in April 2014, the exemption was re-introduced, with smaller coverage. We, therefore, evaluated the influence of this policy change on monthly healthcare utilization in Miyagi prefecture between April 2008 and June 2015. We also evaluated the association between the proportion of people exempted from copayment in each municipality and the difference in healthcare utilization before and after the suspension using multivariable linear regression. Healthcare utilization in Miyagi increased immediately after the institution of the exemption policy and it peaked after one year. In March 2013, just before the suspension, a rapid increment in healthcare utilization was observed, suggesting that the copayment may be a barrier for people in the disaster-affected area to access to healthcare. The exemption policy did help the survivors to use healthcare utilization in Miyagi. After devastating natural disasters, policymakers should guarantee that all survivors can utilize healthcare services on demand.
著者
Jerrold Petrofsky Haneul Lee
出版者
東北ジャーナル刊行会
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.237, no.3, pp.219-226, 2015 (Released:2015-11-03)
参考文献数
61
被引用文献数
1 28

One of the sexual hormones, estrogen, increases elasticity of human connective tissue such as the anterior cruciate ligament during the menstrual cycle in women. In the present investigation, the plantar fascia was investigated to see if there is a difference in elasticity with the menstrual cycle. Fifteen young healthy females in the age range of 18-35 years old with a regular menstrual cycle were tested twice throughout one full menstrual cycle; once during the early follicular phases and once at ovulation. Foot length, while standing on both feet and one foot were used to assess plantar fascia elasticity, ultrasound measured plantar fascia thickness while lying and standing, and posture sway and tremor using a balance platform during 8 different balance tests were assessed to see the impact of elasticity changes. Foot length increased significantly at ovulation compared to menstruation when standing on two feet (p = 0.03) and standing on one foot (p < 0.001). There was also a significant increase in plantar fascia in thinning per kilogram weight applied to the foot at ovulation compared to menstruation (p = 0.014). Associated with this increase in elasticity at ovulation, there was a reduction in balance in the most difficult balance tasks and an increase in tremor during ovulation (p < 0.05). Plantar fascia elasticity change during the menstrual cycle might have effects on posture sway and tremor, which could have a potential risk of falling. Therefore, healthy professionals working with young female adults should recognize these physiological effects.
著者
Hisanori Fukunaga Akinari Yokoya Yasuyuki Taki Kevin M. Prise
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.242, no.1, pp.77-81, 2017 (Released:2017-05-27)
参考文献数
32
被引用文献数
6

On March 11, 2011, a devastating earthquake and subsequent tsunami caused serious damage to areas of the Pacific coast in Fukushima prefecture and prompted fears among the residents about a possible meltdown of the Fukushima Daiichi Nuclear Power Plant reactors. As of 2017, over six years have passed since the Fukushima nuclear crisis and yet the full ramifications of the biological exposures to this accidental release of radioactive substances remain unclear. Furthermore, although several genetic studies have determined that the variation in radiation sensitivity among different individuals is wider than expected, personalized medical approaches for Fukushima victims have seemed to be insufficient. In this commentary, we discuss radiobiological issues arising from low-dose radiation exposure, from the cell-based to the population level. We also introduce the scientific utility of the Integrative Japanese Genome Variation Database (iJGVD), an online database released by the Tohoku Medical Megabank Organization, Tohoku University that covered the whole genome sequences of 2,049 healthy individuals in the northeastern part of Japan in 2016. Here we propose a personalized radiation risk assessment and medical approach, which considers the genetic variation of radiation sensitivity among individuals, for next-step developments in radiological protection.
著者
Ferda Kaleagasioglu Ercan Olcay
出版者
東北ジャーナル刊行会
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.226, no.4, pp.251-258, 2012 (Released:2012-03-28)
参考文献数
66
被引用文献数
6 32

Tendinopathy is a serious health problem and its etiology is not fully elucidated. Among intrinsic and extrinsic predisposing factors of tendinopathy, the impact of therapeutic agents, especially fluoroquinolone (FQ) group antibiotics, is recently being recognized. FQs are potent bactericidal agents widely used in various infectious diseases, including community acquired pneumonia and bronchitis, chronic osteomyelitis, traveler's diarrhea, typhoid fever, shigellosis, chronic bacterial prostatitis, uncomplicated cervical and urethral gonorrhea and prophylaxis of anthrax. FQs have an acceptable tolerability range. However, many lines of evidence for developing tendinitis and tendon rupture during FQ use have resulted in the addition of a warning in patient information leaflets. FQ-induced tendinopathy presents a challenge for the clinician because healing response is poor due to low metabolic rate in mature tendon tissue and tendinopathy is more likely to develop in patients who are already at high risk, such as elderly, solid organ transplant recipients and concomitant corticosteroid users. FQs become photo-activated under exposure to ultraviolet light, and this process results in formation and accumulation of intracellular reactive oxygen species (ROS). The subsequent FQ-related oxidative stress disturbs mitochondrial functions, leading to apoptosis. ROS overproduction also has direct cytotoxic effects on extracellular matrix components. Understanding the mechanisms of the FQ-associated tendinopathy may enable designing safer therapeutic strategies, hence optimization of clinical response. In this review, we evaluate multi-factorial etiology of the FQ-induced tendinopathy and discuss proposed preventive measures such as antioxidant use and protection from natural sunlight and artificial ultraviolet exposure.
著者
Junichiro Hashimoto
出版者
東北ジャーナル刊行会
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.233, no.1, pp.1-8, 2014 (Released:2014-04-12)
参考文献数
73
被引用文献数
3 20

Recent advances in technology have enabled the noninvasive evaluation of pulsatile hemodynamics in the central aorta; namely, central pressure and flow measurements. The central blood pressure represents the true load imposed on the heart, kidney and brain, and the central blood flow influences the local flow into these vital organs. An elevation of the central blood pressure has a direct, adverse impact on the target organ and, thus, the cardiovascular prognosis in patients with hypertension. A decrease in the central blood flow can cause organ dysfunction and failure. The central pressure and flow dynamics were conventionally regarded as unidirectional from the heart to the periphery. However, current evidence suggests that it should be recognized as a bidirectional interplay between the central and peripheral arteries. Specifically, the pressure pulse wave is not only transmitted forward to the periphery but also reflected backward to the central aorta. The flow pulse wave is also composed of the forward and reverse components. Aortic stiffening and arteriolar remodeling due to hypertension not only augment the central pressure by increasing the wave reflection but also may alter the central bidirectional flow, inducing hemodynamic damage/dysfunction in susceptible organs. Therefore, central hemodynamic monitoring has the potential to provide a diagnostic and therapeutic basis for preventing systemic target organ damage and for offering personalized therapy suitable for the arterial properties in each patient with hypertension. This brief review will summarize hypothetical mechanisms for the association between the central hemodynamics and hypertensive organ damage in the heart, kidney and brain.
著者
SEIICHI AONUMA FUMIO ARIJI KOTARO OIZUMI KIYOSHI KONNO
出版者
東北ジャーナル刊行会
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.152, no.2, pp.119-128, 1987 (Released:2006-08-31)
参考文献数
9
被引用文献数
2 2

AONUMA, S., ARIJI, F., OIZUMI, K. and KONNO, K. Electron Microscopy of Pseudomonas aeruginosa Treated with Sulbenicillin and Dibekacin. Tohoku J. exp. Med., 1987, 152 (2), 119-128 - A possible mechanism responsible for the combined effects of sulbenicillin and dibekacin on Pseudomonas aeruginosa TAM 1007 was investigated. The bactericidal activity of the above two drugs in combination was very strong. The regrowth of test strains after removal of the drugs was suppressed markedly, even when they were exposed to sulbenicillin plus dibekacin at a subinhibitory concentration of individual drugs. Sulbenicillin caused elongation of the bacterial cells. At the early stage of elongation, no demonstrable changes of ultrastructure of the cell wall were observed. At the late stage, lysis of the peptidoglycan layer occurred and spheroplast was formed. However, most of the outer membrane of the cell wall remained intact. Sulbenicillin acts upon the peptidoglycan layer, but not on the outer membrane. Thus it is difficult for sulbenicillin alone to cause cell lysis. On the other hand, dibekacin caused destruction of ribosomes and lysis of the outer membrane of the cell wall. Both sulbenicillin and dibekacin act on the cell wall, the former on the peptidoglycan layer (the inner membrane) and the latter on the outer membrane. The combined use of sulbenicillin and dibekacin caused elongation of bacilli and severe destruction of the inner and outer membranes of the cell wall. These morphological changes occurred even when the concentration of the individual drug was lower than its minimum inhibitory concentration (MIC). Furthermore, the cells elongated by sulbenicillin were ruptured easily when treated with dibekacin subsequently. The bacilli treated with dibekacin at a concentration lower than MIC and then treated with sulbenicillin at a concentration lower than MIC showed a marked elongation of the cells, which indicated that the effects of sulbenicillin was enhanced by dibekacin. These findings suggested strongly that sulbenicillin and dibekacin act on cell wall constituents and that their effects were complementary and synergistic.
著者
Hiroyuki Tsuchie Naohisa Miyakoshi Yuji Kasukawa Tomio Nishi Hidekazu Abe Masaaki Takeshima Yoichi Shimada
出版者
東北ジャーナル刊行会
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.230, no.2, pp.83-86, 2013 (Released:2013-06-12)
参考文献数
13
被引用文献数
2 6

Low back pain (LBP) is one of the most common symptoms in outpatient clinics, and abdominal aortic aneurysm (AAA) is one of the causes of LBP. In the present study, we examined the prevalence of chronic LBP in patients with aortic aneurysm. The study included 23 patients with AAA and 23 patients with thoracic aortic aneurysm (TAA); all of them visited a regional center hospital in Akita, Japan. A total of 207 hypertension patients were also enrolled as a control. Chronic LBP was defined in patients who visited the orthopedic outpatient clinic for the LBP treatment for more than three months. The prevalence of chronic LBP in the AAA group (52.2%) was significantly higher than that in the TAA (17.4%, P < 0.05) or hypertension patients (11.6%, P < 0.01). The rate of a trigger point (TP) injection was significantly higher in the AAA group or the TAA group than that in hypertension patients (P < 0.01, P < 0.05), but there was no significant difference between the AAA and TAA groups. The TP injection represents an injection of local anesthesia to the low back muscles. We also evaluated the involvement of various factors in LBP caused by AAA, such as age, gender, blood pressure, the existence of dissection, and the maximum diameter of AAA, but none of them showed significant relationship to LBP. The prevalence of LBP is high in AAA patients, and doctors who treat chronic LBP should be aware of AAA as a potential cause of LBP.
著者
James P. Butler Masahiko Fujii Hidetada Sasaki
出版者
東北ジャーナル刊行会
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.227, no.3, pp.203-210, 2012 (Released:2012-06-27)
参考文献数
96
被引用文献数
12 17

Our new lessons of nurturing life to make happiness and well-being of geriatric patients suggest comprise several important steps. First, geriatric patient care should not be delegated to specialists who focus on individual organ system. Instead, we should respond to the patient's condition based on comprehensive assessment to identify the single pathogenesis. Second, we should appreciate that the behavioral and psychological symptoms of dementia (BPSD) often reflect the behavioral and psychological symptoms of the caregiver (BPSC), and in particular the caregiver's attitude. Third, pleasant stimulations to the limbic system should receive more emphasis than attempting brain training in atrophied portions of the neocortex. Fourth, we should aim not for “successful aging,” but for “balanced aging.” Fifth, we should rely less on drug-based therapy and utilize more non-pharmacologic approaches to appropriate therapy. Geriatric patients should be cared for based on our new lessons of nurturing life rather than the heavily medicalized treatment modalities that are in wide use today.
著者
Susumu Ogawa Takaaki Abe Kazuhiro Nako Masashi Okamura Miho Senda Takuya Sakamoto Sadayoshi Ito the DIMS study group
出版者
東北ジャーナル刊行会
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.231, no.1, pp.63-74, 2013 (Released:2013-09-25)
参考文献数
37
被引用文献数
4 19

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are ω3-polyunsaturated fatty acids mainly contained in the blue-backed fish oil, and are effective in decreasing the lipids disorder and the cardiovascular incidence among diabetic patients. Moreover, it has been suggested that EPA and DHA may improve the insulin resistance and glucose metabolism. However, the clinical effects of EPA and DHA on glucose metabolism remain unclear. We aimed to clarify the effects of EPA/DHA treatment on glycemic control in type 2 diabetes mellitus. This study was a multicenter prospective randomized controlled trial involving 30 elderly type 2 diabetic patients on a liquid diet. Their exercises were almost zero and the content of their meals was strictly managed and understood well. Therefore, the difference by the individual's life was a minimum. The subjects were divided into two groups: those receiving EPA/DHA-rich liquid diet [EPA/DHA (+)] or liquid diet lacking EPA/DHA [EPA/DHA (−)]. Changes in factors related to glucose and lipid metabolism were assessed after the three-month study. Serum concentrations of EPA rose in EPA/DHA (+), although the levels of DHA and fasting C-peptide remained unchanged in EPA/DHA (+). In addition, there was a significant decline in the fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), fasting remnant-like particles and apolipoprotein (apo) B in EPA/DHA (+), compared with the values in EPA/DHA (−). EPA/DHA-rich diet might improve glucose metabolism in elderly type 2 diabetic patients on a liquid diet. This phenomenon may be due to the improved insulin resistance mediated by the rise in serum EPA concentrations.
著者
Chayanin Angthong Wirana Angthong Thos Harnroongroj Thossart Harnroongroj
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.226, no.2, pp.129-135, 2012 (Released:2012-01-26)
参考文献数
26
被引用文献数
1 1

Little is known about the effect of a subsequent osteoporotic vertebral compression fracture on the survival rate of patients with a previous hip fracture. In this study, we aimed to compare the survival rates of hip fracture patients with and without subsequent osteoporotic vertebral compression fractures and determine the risk factors associated with subsequent fracture. During 2000-2008, 933 initial hip fracture patients were reviewed and divided into two groups: subsequent fracture group (160 patients) and single hip fracture group (i.e., no subsequent fracture; 773 patients). All information pertaining to their most recent fracture event(s), including mortality causes/rates, were recorded. Differences in mortality rates and hazard ratios (HRs) between the two groups were also analyzed. The 1-year and 1-to-5-year mortality rates were 1.3% and 1.9%, respectively, in the subsequent fracture group, and 4.7% and 1.4%, respectively, in the single hip fracture group, with no significant differences observed. Interestingly, the HR for mortality was significantly higher in the single hip fracture group than in the subsequent fracture group (p < 0.05). The significant risk factors for subsequent fractures were identified as knee osteoarthritis, neurological disease, and an initial hip fracture with intertrochanteric involvement. Our findings indicate that the occurrence of a vertebral compression fracture after an initial hip fracture does not greatly impact patient survival. Conversely, patients presenting with a single hip fracture have a significantly higher mortality-HR, indicating that single hip fracture patients without subsequent fracture should be provided with the same standard of care as patients with subsequent fractures.
著者
Hiroyuki Yamamoto Kyoko Yamamoto Katsumi Yoshida Chiyohiko Shindoh Kyoko Takeda Masami Monden Hiroko Izumo Hiroyuki Niinuma Yutaro Nishi Koichiro Niwa Yasuhiro Komatsu
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.237, no.3, pp.201-207, 2015 (Released:2015-10-24)
参考文献数
24
被引用文献数
2 2

Chronic kidney disease (CKD) is a global public health issue, and strategies for its early detection and intervention are imperative. The latest Japanese CKD guideline recommends that patients without diabetes should be classified using the urine protein-to-creatinine ratio (PCR) instead of the urine albumin-to-creatinine ratio (ACR); however, no validation studies are available. This study aimed to validate the PCR-based CKD risk classification compared with the ACR-based classification and to explore more accurate classification methods. We analyzed two previously reported datasets that included diabetic and/or cardiovascular patients who were classified into early CKD stages. In total, 860 patients (131 diabetic patients and 729 cardiovascular patients, including 193 diabetic patients) were enrolled. We assessed the CKD risk classification of each patient according to the estimated glomerular filtration rate and the ACR-based or PCR-based classification. The use of the cut-off value recommended in the current guideline (PCR 0.15 g/g creatinine) resulted in risk misclassification rates of 26.0% and 16.6% for the two datasets. The misclassification was primarily caused by underestimation. Moderate to substantial agreement between each classification was achieved: Cohen’s kappa, 0.56 (95% confidence interval, 0.45-0.69) and 0.72 (0.67-0.76) in each dataset, respectively. To improve the accuracy, we tested various candidate PCR cut-off values, showing that a PCR cut-off value of 0.08-0.10 g/g creatinine resulted in improvement in the misclassification rates and kappa values. Modification of the PCR cut-off value would improve its efficacy to identify high-risk populations who will benefit from early intervention.
著者
TOSHIHIRO FUJIOKA YASUHIRO SAKAMOTO GORO MIMURA
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.141, no.Suppl, pp.453-463, 1983 (Released:2008-11-28)
参考文献数
16
被引用文献数
5 10

An investigation was undertaken to evaluate the antiarrhythmic effect of CoQ10 on VPBs using the Holter ECG, in 27 patients with no clinical findings of organic cardiopathies. As a result, the effect of CoQ10 on VPBs was considered beneficial in 6 (22%) of 27 cases, consisting of 1 patient with hypertension and 5 patients with DM. Even in the remaining 2 patients with DM, the frequency of VPBs was reduced by 50% or more during treatement with CoQ10. The mean reduction of VPBs frequency in the 5 responders plus these 2 patients with DM was 85.7%. These findings suggest that CoQ10 exhibits an effective antiarrhythmic action not merely on organic heart disease but also on VPBs supervening on DM.
著者
Ryuji Shioji Shozo Rikimaru Hiroshi Ito
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.93, no.1, pp.63-69, 1967 (Released:2008-11-28)
参考文献数
8
被引用文献数
1 1

Urinary citrate output was studied in 5 cases of primary aldosteronism, in 3 of Addison's disease and in 8 of normal subjects. The urinary citrate output was decreased in 4 of 5 cases of primary aldosteronism, and the citrate output could not be normalized by removal of adrenocortical adenoma. In patients with primary aldosteronism citrate excretion was somewhat increased by admini-stration of potassium chloride, but rather decreased by spironolactone. In these patients urinary citrate output could not be correlated with either plasma CO2 content or plasma potassium concentration. The low urinary citrate excretion in primary aldosteronism may not be satisfactorily explained either by direct action of aldosterone on the kidney or by intracellular acidosis.
著者
Hiroaki Shimokawa Tomohiko Shindo Aiko Ishiki Naoki Tomita Sadamitsu Ichijyo Tasuku Watanabe Takashi Nakata Kumiko Eguchi Yoku Kikuchi Takashi Shiroto Jun Takahashi Satoshi Yasuda Hiroyuki Arai
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.258, no.3, pp.167-175, 2022 (Released:2022-10-25)
参考文献数
30
被引用文献数
8

The prevalence of Alzheimer’s disease (AD) has been rapidly increasing worldwide. We have developed a novel angiogenic therapy with low-intensity pulsed ultrasound (LIPUS), which is effective and safe in animal models of AD and vascular dementia. We performed two trials of LIPUS therapy for AD (mild cognitive impairment due to AD and mild AD); a roll-in open trial for safety, and a randomized, double-blind, placebo-controlled (RCT) trial for efficacy and safety. The LIPUS therapy was performed for whole brain through the bilateral temporal bones for one hour 3 times a week as one session under the special conditions (1.3 MPa, 32 cycles, 5% duty cycle) we identified. The LIPUS therapy was performed for one session in the roll-in trial, and 6 sessions in the RCT trial with 3-month intervals for 1.5 years. The primary endpoint was ADAS-J cog scores. The RCT trial was terminated prematurely due to the COVID-19 pandemic. In the roll-in trial (N = 5), no adverse effects were noted. In the RCT trial (N = 22), the worsening of ADAS-J cog scores tended to be suppressed in the LIPUS group compared with the placebo group at week 72 (P = 0.257). When responders were defined as those with no worsening of ADAS-J cog scores at week 72, the prevalence was 50% (5/10) and 0% (0/5) in the LIPUS and placebo groups, respectively (P = 0.053). No adverse effects were noted. These results suggest that the LIPUS therapy is safe and tends to suppress cognitive impairment although a next pivotal trial with a large number of subjects is warranted.
著者
Andros Theo Tracy Masebe Yasuhiro Suzuki Haruhisa Kikuchi Shoko Wada Chikwelu Larry Obi Pascal Obong Bessong Motoki Usuzawa Yoshiteru Oshima Toshio Hattori
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.217, no.2, pp.93-99, 2009 (Released:2009-02-11)
参考文献数
38
被引用文献数
35 40

The biodiversity of medicinal plants in South Africa makes them rich sources of leading compounds for the development of novel drugs. Peltophorum africanum (Fabaceae) is a deciduous tree widespread in South Africa. The stem bark has been traditionally employed to treat diarrhoea, dysentery, sore throat, wounds, human immunodeficiency virus/ acquired immune deficiency syndrome (HIV/AIDS), venereal diseases and infertility. To evaluate these ethnobotanical clues and isolate lead compounds, butanol and ethyl acetate extracts of the stem bark were screened for their inhibitory activities against HIV-1 using MAGI CCR5+ cells, which are derived from HeLa cervical cancer cells and express HIV receptor CD4, a chemokine receptor CCR5 and HIV-LTR-β- galactosidase. Bioassay-guided fractionation using silica gel chromatography was also conducted. The ethyl acetate and butanol extracts of the stem bark of Peltophorum africanum showed inhibitory activity against HIV-1, CXCR4 (X4) and CCR5 (R5) tropic viruses. The ethyl acetate and butanol extracts yielded previously reported anti-HIV compounds, (+)-catechin, a flavonoid, and bergenin, a C-galloylglycoside, respectively. Furthermore, we identified betulinic acid from the ethyl acetate fraction for the first time. The fractions, which contained betulinic acid, showed the highest selective index. We therefore describe the presence of betulinic acid, a not well-known anti-HIV compound, in an African medicinal herb, which has been used for therapy, and claim that betulinic acid is the predominant anti-HIV-1 constituent of Peltophorum africanum. These data suggest that betulinic acid and its analogues could be used as potential therapeutics for HIV-1 infection.