1.Interleukin-34 cancels anti-tumor immunity by PARP inhibitor
Takayoshi NAKAMURA ; Nabeel KAJIHARA ; Naoki HAMA ; Takuto KOBAYASHI ; Ryo OTSUKA ; Nanumi HAN ; Haruka WADA ; Yoshinori HASEGAWA ; Nao SUZUKI ; Ken-ichiro SEINO
Journal of Gynecologic Oncology 2023;34(3):e25-
Objective:
Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME).
Methods:
In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34.
Results:
We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34.
Conclusion
These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.
2.Pranlukast reduces asthma exacerbations during autumn especially in 1- to 5-year-old boys
Yoshinori MORITA ; Eduardo CAMPOS ALBERTO ; Shuichi SUZUKI ; Yoshinori SATO ; Akira HOSHIOKA ; Hiroki ABE ; Kimiyuki SAITO ; Toshikazu TSUBAKI ; Mana HARAKI ; Akiko SAWA ; Yoshio NAKAYAMA ; Hiroyuki KOJIMA ; Midori SHIGETA ; Fumiya YAMAIDE ; Yoichi KOHNO ; Naoki SHIMOJO
Asia Pacific Allergy 2017;7(1):10-18
BACKGROUND: Leukotriene receptor antagonists have been used to prevent virus-induced asthma exacerbations in autumn. Its efficacy, however, might differ with age and sex. OBJECTIVE: This study aimed to investigate whether pranlukast added to usual asthma therapy in Japanese children during autumn, season associated with the peak of asthma, reduces asthma exacerbations. It was also evaluated the effect of age and sex on pranlukast's efficacy. METHODS: A total of 121 asthmatic children aged 1 to 14 years were randomly assigned to receive regular pranlukast or not according to sex, and were divided in 2 age groups, 1–5 years and 6–14 years. The primary outcome was total asthma score calculated during 8 weeks by using a sticker calendar related to the days in which a child experienced a worsening of asthma symptoms. This open study lasted 60 days from September 15 to November 14, 2007. RESULTS: Significant differences in pranlukast efficacy were observed between sex and age groups. Boys aged 1 to 5 years had the lower total asthma score at 8 weeks (p = 0.002), and experienced fewer cold episodes (p = 0.007). There were no significant differences between pranlukast and control group in total asthma score at 8 weeks (p = 0.35), and in the days in which a child experienced a worsening of asthma symptoms (p = 0.67). CONCLUSION: There was a substantial benefit of adding pranlukast to usual therapy in asthmatic children, especially in boys aged 1 to 5 years, during autumn season.
Asian Continental Ancestry Group
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Asthma
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Child
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Child, Preschool
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Humans
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Leukotriene Antagonists
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Seasons
3.Geographical Information Analysis of Difficulty of Access to Hospital to the Elderly Living in Mountainous Areas
Masayoshi IDE ; Tomihiro HAYAKAWA ; Reiko KASHIWADA ; Eriko YONEDA ; Nozomu ANDO ; Toshitaka WATARIGUCHI ; Yoshinori SUZUKI ; Shinya KOBAYASHI ; Mizuo TSUZUKI ; Yoshie ESAKI ; Ken KATO ; Hiroshi AMANO ; Makoto MIYAJI
Journal of the Japanese Association of Rural Medicine 2013;61(4):582-601
We examined how difficult it would be for the elderly living in mountainous areas to go to the nearest hospital using a Voronoi tessellation representing the mathematical concept of neighborhood. We defined the index of the nursing-care capacity for the elderly as the ratio of the number of caregivers to the number of the elderly receiving nursing-care.
The mean age of those who drive to the hospital by themselves worked out at 70±9.8 years. Meanwhile, that of those who go to the hospital by bus or taken to hospital in a car driven by a family member came to 80±7.0years. The latter was significantly older than the former.
The areas of the Voronoi tessellation generated by patients' places of residence were divided into three groups according to the size. The plots of these three groups of the the places of residence on the map had a three-layer and doughnut-like structure, i. e., inner-, middle-, and outer-layer.
The index of the nursing-care capacity in 2008 was less than 1.0 for the patients under 80 years of age. This means that when those who were at the age of 50 in 2008 become old and need nursing-care, access to the hospital will become harder to them than at present. For those who are over 80 years of age and live in the outer layer that is far away from arterial road, it will be almost impossible.
These findings suggest that outpatient care with transportation assistance by a family member at present should be reconsidered because of the future lack of care personnel. It would also be necessary to consider the welfare of older people from the geographical point of view in order to manage the problems concerning the various physical and sociological difficulties of the elderly.
4.A Case of Surgical Treatment for Aortic Root Dissection after Full Aortic Root Replacement with Stentless Aortic Valve
Nobuaki Suzuki ; Tadaaki Koyama ; Katsuhiro Hosoyama ; Yoshinori Nakahara ; Yuusuke Tsukioka ; Takuya Miyazaki ; Ken Furuhata ; Tomohiro Iwakura ; Takeyuki Kanemura ; Shigehiko Yoshida
Japanese Journal of Cardiovascular Surgery 2012;41(4):185-187
A 84-year-old woman underwent aortic root replacement with stentless bioprosthesis and coronary artery bypass grafting. Four years later, she presented with dyspnea. Transthoracic echocardiography revealed aortic regurgitation, dilation and dissection of the sinus of Valsalva. A Bentall operation was performed by using prosthetic graft and bioprosthetic valve. Intimal tear caused the aortic wall dissection and aneurysm of the Freestyle valve.
7.Cooperation between Hospital and Nursing Home by E-mail
Masayoshi IDE ; Tomihiro HAYAKAWA ; Yoshinori SUZUKI ; Shinya KOBAYASHI ; Tatsuya FUKUTOMI ; Mizuo TSUZUKI ; Hiroe ESAKI
Journal of the Japanese Association of Rural Medicine 2010;59(1):1-16
After 1985, the decrease in domestic nursing power progressed gradually. The care for the elderly shifted from domestic private nursing to public nursing-care services when the long-term nursing-care insurance law was enacted in 2000. Because many of the elderly receiving nursing care suffer from chronic ailments of hypertension or the consequences of cerebrovascular disease, etc., cooperation between hospitals and nursing homes is necessary and indispensable. We began exchanging information by E-mail on a trial basis with a special elderly nursing home in April 2009. We aimed to integrate medical care and nursing by sharing medical and nursing information. We concluded that the use of E-mail could serve our purpose. The reason why we reached this conclusion is as follows:The mechanism of the information transmission by E-mail, that also relates to semiotics and narratology, is related to the essence of the description. This mechanism functions as a tool for mutual understanding among hospitals, nursing homes, and families. This also functions as a device to make the medical and nursing experience join. As a result, this mechanism enables the elderly to escape death as dying of sickness in the hospital and to die a natural death in the course of nursing. It is an easy method that can be introduced at a low cost for the purpose of establishing cooperation in medical and nursing care among hospitals, clinics, nursing homes, and nursing support centers, etc. especially in medically underserved remote areas.
8.Relationship between dietary habits and urinary concentrations of 3-phenoxybonzoic acid in a middle-aged and elderly general population in Japan.
Akiko KIMATA ; Takaaki KONDO ; Jun UEYAMA ; Kanami YAMAMOTO ; Michihiro KAMIJIMA ; Koji SUZUKI ; Takashi INOUE ; Yoshinori ITO ; Nobuyuki HAMAJIMA
Environmental Health and Preventive Medicine 2009;14(3):173-179
OBJECTIVESThe ingestion of pesticides in the daily diet is assumed to be the main modality of pesticide exposure for most people. A widely used class of pesticides in agricultural or residential settings is pyrethroid. We have examined the relationship between the intake frequency of selected items of vegetables and fruits and urinary metabolites of pyrethroid pesticides in a healthy general population.
METHODSA total of 535 residents (184 men and 351 women) who attended a healthcare checkup program conducted in a rural area of Hokkaido, Japan, in August 2005 provided informed consent for their spot urine samples to be used for the determination of 3-phenoxybenzoic acid (3-PBA) levels. They also completed a self-administered questionnaire regarding the intake frequency of 12 food items. The concentrations of creatinine-corrected 3-PBA were predicted by the intake frequency of each item, using analysis-of-covariance models to adjust for age, sex, body mass index, and drinking and smoking status.
RESULTSBoth a significant association between the 3-PBA concentration and the frequency of tomato consumption and a significant positive linear trend was found in female subjects. In contrast, no such association was found in the male subjects.
CONCLUSIONSThe frequency of tomato consumption was confirmed to strongly predict the urinary pyrethroid metabolite levels in the general population-presumably because tomatoes are most often consumed raw and unpeeled (more so than all other vegetables and fruits analyzed in the current study). However, it should be noted that the 3-PBA levels, even among those subjects with the highest consumption of tomatoes, were far below the levels of toxicological significance, although the health consequences from long-term low-level exposure to pyrethroid requires further exploration.
9.Association of serum NO( x ) level with clustering of metabolic syndrome components in middle-aged and elderly general populations in Japan.
Jun UEYAMA ; Takaaki KONDO ; Ryota IMAI ; Akiko KIMATA ; Kanami YAMAMOTO ; Koji SUZUKI ; Takashi INOUE ; Yoshinori ITO ; Ken-Ichi MIYAMOTO ; Takaaki HASEGAWA ; Nobuyuki HAMAJIMA
Environmental Health and Preventive Medicine 2008;13(1):36-42
OBJECTIVESThe aim of this study was to determine whether the serum nitrite plus nitrate (NO( x )) level correlates with biomarkers that are known components of the metabolic syndrome (MetS).
METHODSSerum NO( x ) levels were measured using a commercial kit in 608 Japanese men and women between the ages of 39 and 85 years. Multivariate adjustments for age, smoking status, alcohol consumption and exercise were made in the analysis of covariance (ANCOVA). The components of the metabolic syndrome were defined based on the following criteria: body mass index (BMI) >/=25.0 kg/m(2), glycated hemoglobin (HbA1c) >/=5.6%, systolic blood pressure >/=130 mmHg or diastolic blood pressure >/=85 mmHg, high-density lipoprotein-cholesterol (HDL-C) =1.03 mmol/l for men and =1.29 mmol/l for women and triglyceride >/=1.69 mmol/l.
RESULTSThe logarithmically transformed age-adjusted serum NO( x ) (lnNO( x )) value was significantly higher in the low HDL-C group (1.76 +/- 0.05 mumol/l; p < 0.05) than MetS component groups (1.65 +/- 0.01 mumol/l) in men, but no difference was found in women. The means of serum lnNO( x ) after multivariate adjustment were 1.64, 1.65, 1.64, 1.66, and 1.81 mumol/l for 0, 1, 2, 3, and 4-5 MetS components for all subjects, respectively. The results of ANCOVA confirmed that the serum lnNO( x ) level was significantly correlated with the clustering of MetS components in both men and women (p < 0.0001 for trend).
CONCLUSIONOur results suggest that an increase in the clustering of MetS components was associated with the increase in serum NO levels in our general population.
10.Physiological Changes by Half-body Bathing
Ritsuko YAMAZAKI ; Yasuki HONDA ; Ushio HARADA ; Yuji SUZUKI ; Yoshinori OHTSUKA
The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine 2007;70(3):165-171
Purpose
Half body bathing is popular among young women as well as elderly people. As a matter of fact, it is reported that half body bathing has a smaller burden than whole-body bathing from the point of physical influence. To clarify the relation between bathing habitude and health maintenance, that is, as an approach to general understanding the physiological effects by repeating bathing stimuli, the physiological changes by continuing half body bathing were studied.
Methods
Half body bathing was repeated for 4 weeks in healthy female subjects (N=10, age: 30.1±4.8, height: 160.4±6.1cm, weight: 55.6±7.0kg, body mass index: 20.9±1.6kg/m2, mean±SD).
Bathing was performed for 30 minutes and 3times a week, with a level of epigastrium without immersing arms. Changes of blood flow and energy expenditure were measured during bathing at 0W and 4W.
Results and Discussion
By continuing bathing, blood flow increased more rapidly and higher during bathing, in addition, resting energy expenditure increased by 200kcal/day with a significant difference.
From these findings, it is assumed that repeated half-body bathing enhances the increase of blood flow through repeating thermal stimuli, which leads to elevated basal metabolism.


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