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941.
Advanced Glycation End Products in Alzheimer’s Disease and Other Neurodegenerative Diseases
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Nobuyuki Sasaki Ryo Fukatsu Kayo Tsuzuki Yorihide Hayashi Taku Yoshida Nobuhiro Fujii Takao Koike Ikuro Wakayama Richard Yanagihara Ralph Garruto Naoji Amano Zenji Makita 《The American journal of pathology》1998,153(4):1149-1155
Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer’s disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid β protein (Aβ), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer’s disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick’s disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer’s brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but Aβ negative, and the vessels without CAA often showed AGE immunoreactivity. In Alzheimer’s disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick’s bodies in Pick’s disease and granulovacuolar degeneration in various neurodegenerative diseases were also AGE positive. In non-Alzheimer neurodegenerative diseases, senile plaques and NFTs showed similar findings to those in Alzheimer’s disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer’s disease. 相似文献
942.
943.
Mao Hagihara Hideo Kato Toshie Sugano Hayato Okade Nobuo Sato Yuichi Shibata Daisuke Sakanashi Nobuhiro Asai Yusuke Koizumi Hiroyuki Suematsu Yuka Yamagishi Hiroshige Mikamo 《International journal of antimicrobial agents》2021,57(5):106330
BackgroundCarbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) are difficult to treat and are a serious public health threat. Nacubactam (NAC) is a novel non-β-lactam diazabicyclooctane β-lactamase inhibitor with in vitro activity against some Enterobacterales expressing classes of β-lactamases.MethodsThe antimicrobial efficacy of meropenem (MEM), cefepime (FEP), and aztreonam (ATM), each in combination with NAC, were assessed in vitro and in vivo against Klebsiella pneumoniae and Escherichia coli. Ten isolates, including CRE and/or CPE with β-lactamase genes, were used in this study. The relationship between phenotype and in vivo efficacy was assessed in a murine neutropenic thigh-infection model. Efficacy was determined by the change in bacterial quantity.ResultsThe results of the in vitro study showed the minimum inhibitory concentrations of the combination of NAC with either MEM, FEP, or ATM in a 1:1 ratio were 2 to >128-fold lower than those of MEM, FEP, or ATM alone against CRE+ isolates. In addition, combinations of β-lactams and NAC administered in the murine thigh-infection model showed greater efficacy against CRE+/CPE+, CRE+/CPE-, and CRE-/CPE+ isolates harboring various β-lactamase genes (IMP-1, IMP-6, KPC, DHA-1, or OXA-48) compared with MEM, FEP, ATM, and NAC alone.ConclusionMEM, FEP, or ATM in combination with NAC showed potent in vivo antimicrobial activity in a murine thigh-infection model caused by K. pneumoniae and E. coli, including CRE and/or CPE isolates. These findings indicate that these combinations of β-lactams and NAC are potential candidates for the treatment of CRE and/or CPE infections. 相似文献
944.
Masayoshi Fukushima Hiroyuki Oka Nobuhiro Hara Yasushi Oshima Hirotaka Chikuda Sakae Tanaka Katsushi Takeshita Ko Matsudaira 《Journal of orthopaedic science》2017,22(3):411-414
Background
A few cohort studies have determined which patients with lumbar spinal stenosis are likely to need surgery because of the deterioration of symptoms. However, there are still insufficient data regarding the management of lumbar spinal stenosis due to lack of prognostic factors associated with the need for surgery. The purpose of this study was to identify the prognostic factors associated with the need for surgical treatment in patients with lumbar spinal stenosis.Methods
Patients with lumbar spinal stenosis from our hospital and related facilities were enrolled. Eligibility criteria were as follows: age 50–85 years and the patient's conditions met the definition of lumbar spinal stenosis; the presence of neurogenic intermittent claudication caused by numbness and/or pain in the lower limbs; and magnetic resonance imaging-confirmed symptomatic LSS. We followed 274 patients (151 men; mean age, 71 ± 7.4 years) for 3 years to identify prognostic factors. We used a multivariate logistic regression model to investigate the association between the indication for surgical treatment (within 3 years) and age, sex, complications, depression, illness duration, the presence of cauda equina symptoms, and the presence of degenerative spondylolisthesis/scoliosis.Results
In the survey conducted 3 years after treatment, 185 patients responded (follow-up rate 67.5%). In 82 patients, surgery was performed during the follow-up period. The multivariate logistic regression model showed that the presence of cauda equina symptoms and the presence of degenerative spondylolisthesis/scoliosis were significantly associated with the indication for surgical treatment within 3 years.Conclusions
This study showed that the presence of cauda equina symptoms and degenerative spondylolisthesis/scoliosis were prognostic factors associated with the indication for surgery in patients with lumbar spinal stenosis. 相似文献945.
Chie?TakasuEmail author Wubetu?Gizachew?Yismaw Nobuhiro?Kurita Kozo?Yoshikawa Hideya?Kashihara Toru?Kono Mitsuo?Shimada 《Surgery today》2017,47(10):1287-1294
Purpose
We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT.Methods
Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i.p. for 2 days), and the CPT-11 and TU-100 co-treated group (1000 mg/kg, p.o. for 5 days). All of the rats were sacrificed on day 6 and their tissues were collected.Results
CPT-11 and TU-100 co-treatment improved CPT-11 the related cytotoxicity in vitro. All CPT-11-treated rats developed different grades of diarrhea and BT was observed in 80% of the rats. CPT-11 caused a significant increase in the expression of TLR4, IL-6, TNF-α, IL-1β and caspase-3 mRNAs in the large intestine. The expression of tight junction (TJ) marker mRNAs (occludin, claudin-1 and 4, and ZO-1) was significantly decreased in comparison to the control group. TU-100 co-treatment significantly reversed diarrhea, BT, and the expression of TLR2, IL-6, TNF-α, IL-1β and caspase-3, and improved the expression of occludin, claudin-4 and ZO-1.Conclusions
TU-100 can suppress the adverse effects associated with CPT-11 and improve the function of the TJ. It is possible that this occurs through the TLR pathway.946.
947.
Chiyomi Egawa Kouichi Hirokaga Shintaro Takao Kazuhiko Yamagami Masaru Miyashita Masashi Baba Shigetoshi Ichii Muneharu Konishi Yuichiro Kikawa Junya Minohata Toshitaka Okuno Keisuke Miyauchi Kazuyuki Wakita Hirofumi Suwa Takashi Hashimoto Masayuki Nishino Takashi Matsumoto Toshiharu Hidaka Yutaka Konishi Yoko Sakoda Akihiro Miya Masao Mitsunobu Hidefumi Nishikawa Seishi Kono Ikuo Kokufu Isao Sakita Koushiro Kitatsuji Koushi Oh Yasuo Miyoshi 《International journal of clinical oncology / Japan Society of Clinical Oncology》2016,21(2):262-269
Background
Endocrine treatment-related adverse events have a strong impact on patients’ quality of life and sometimes result in treatment discontinuation. Since joint symptoms are the most frequently recognized side effect of aromatase inhibitors, evaluation of associated risk factors may yield significant findings.Patients and methods
A total of 391 postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled from 28 centers for assessment of patient-reported outcomes (PROs) in this prospective cohort study (SAVS-JP, UMIN000002455). Patients completed the self-report questionnaire at baseline and after 3, 6, 9, and 12 months of treatment for evaluation of frequency of treatment-related joint symptoms (arthralgia, decrease in range of joint motion, and joint stiffness).Results
We obtained PROs from 362 patients (92.6 %) at baseline and at one or more subsequent points. New or worsening from baseline of joint symptoms were reported by 260 patients (71.8 %). More than 90 % of the symptoms were mild or moderate and nearly 80 % had occurred by 6 months. Multivariate analysis showed that a short time span after menopause [odds ratio (OR) 0.95, 95 % confidence interval (CI) 0.90–0.99; P = 0.02] and adjuvant chemotherapy (OR 2.29, 95 % CI 1.06–4.95; P = 0.03) were significant independent risk factors for joint symptoms. No significant relationships between body mass index (BMI) and joint symptoms were identified. Eighteen patients discontinued treatment during the 1st year and eight of them reported joint symptoms.Conclusion
Taking into consideration that PROs may yield higher prevalence rates than physician ratings for symptoms published in pivotal clinical trials, we found that a short time span after menopause and use of adjuvant chemotherapy, but not high BMI, were significantly associated with joint symptoms. These findings might prove useful for counseling before initiating treatment with adjuvant aromatase inhibitors in postmenopausal Japanese women.948.
Cetuximab delivery and antitumor effects are enhanced by mild hyperthermia in a xenograft mouse model of pancreatic cancer
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![点击此处可从《Cancer science》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ryoichi Miyamoto Tatsuya Oda Shinji Hashimoto Tomohiro Kurokawa Yuki Inagaki Osamu Shimomura Yusuke Ohara Keiichi Yamada Yoshimasa Akashi Tsuyoshi Enomoto Mikio Kishimoto Hideto Yanagihara Eiji Kita Nobuhiro Ohkohchi 《Cancer science》2016,107(4):514-520
Even with current promising antitumor antibodies, their antitumor effects on stroma‐rich solid cancers have been insufficient. We used mild hyperthermia with the intent of improving drug delivery by breaking the stromal barrier. Here, we provide preclinical evidence of cetuximab + mild hyperthermia therapy. We used four in vivo pancreatic cancer xenograft mouse models with different stroma amounts (scarce, MIAPaCa‐2; moderate, BxPC‐3; and abundant, Capan‐1 and Ope‐xeno). Cetuximab (1 mg/kg) was given systemically, and the mouse leg tumors were concurrently heated using a water bath method for 30 min at three different temperatures, 25°C (control), 37°C (intra‐abdominal organ level), or 41°C (mild hyperthermia) (n = 4, each group). The evaluated variables were the antitumor effects, represented by tumor volume, and in vivo cetuximab accumulation, indirectly quantified by the immunohistochemical fluorescence intensity value/cell using antibodies against human IgG Fc. At 25°C, the antitumor effects were sufficient, with a cetuximab accumulation value (florescence intensity/cell) of 1632, in the MIAPaCa‐2 model, moderate (1063) in the BxPC‐3 model, and negative in the Capan‐1 and Ope‐xeno models (760, 461). By applying 37°C or 41°C heat, antitumor effects were enhanced shown in decreased tumor volumes. These enhanced effects were accompanied by boosted cetuximab accumulation, which increased by 2.8‐fold (2980, 3015) in the BxPC‐3 model, 2.5‐ or 4.8‐fold (1881, 3615) in the Capan‐1 model, and 3.2‐ or 4.2‐fold (1469, 1922) in the Ope‐xeno model, respectively. Cetuximab was effective in treating even stroma‐rich and k‐ras mutant pancreatic cancer mouse models when the drug delivery was improved by combination with mild hyperthermia. 相似文献
949.
Transnasal ultrathin endoscopy for placement of a long intestinal tube in patients with intestinal obstruction 总被引:1,自引:1,他引:0
Sato R Watari J Tanabe H Fujiya M Ueno N Konno Y Ishikawa C Ito T Moriichi K Okamoto K Maemoto A Chisaka K Kitano Y Matsumoto K Ashida T Kono T Kohgo Y 《Gastrointestinal endoscopy》2008,67(6):953-957
BACKGROUND: The technical difficulties related to the insertion of a long intestinal tube into the jejunum under fluoroscopy present a considerable problem in patients with an intestinal obstruction. OBJECTIVE: To evaluate the usefulness of endoscopic long intestinal-tube placement with the ultrathin esophagogastroduodenoscope (UT-EGD). DESIGN: A prospective randomized clinical trial was conducted. PATIENTS: Twenty-eight consecutive patients who presented with an intestinal obstruction were included in the study. INTERVENTION: The UT-EGD was inserted nasally into at least the second portion of the duodenum or beyond. After a guidewire was introduced through the working channel, with fluoroscopic guidance, the UT-EGD itself was carefully removed with the guidewire left in place. Next, a hydrophilic intestinal tube was advanced over the guidewire into the jejunum, and then the guidewire was removed. MAIN OUTCOME MEASUREMENTS: Primary end points are the total procedure time, the radiation exposure time, and the rate of complications, all compared with the conventional method. RESULTS: The mean (+/-SD) total procedure time was 18.7 +/- 8.4 minutes for the UT-EGD method and 39.5 +/- 15.0 minutes for the conventional method, with a significant time difference between the 2 methods (P < .0005). The mean (+/-SD) radiation exposure time was also shorter with the UT-EGD method (11.1 +/- 6.0 minutes) than with the conventional method (30.3 +/- 13.7 minutes) (P < .0005). There were no complications, except for mild nasal bleeding with each method. CONCLUSIONS: The UT-EGD method has definite advantages in the placement of a long intestinal tube for patients with an intestinal obstruction in comparison with the conventional method. 相似文献
950.
Increased lipoprotein-associated PLA(2) (Lp-PLA(2)) predicts the future development of cardiovascular diseases. Although lysophosphatidylcholine (lyso-PC) produced by Lp-PLA(2) may contribute to its proatherogenic activity, the relation between Lp-PLA(2) and lyso-PC content in LDL remains unclarified. We determined the correlation between lyso-PC content in LDL and serum concentrations of Lp-PLA(2), chemokines, oxidative and inflammatory markers and microvascular complications in 32 patients with type 2 diabetes mellitus free of macroangiopathy. We also investigated the effect of simvastatin treatment on Lp-PLA(2) and lyso-PC content in 26 hypercholesterolemic patients with type 2 diabetes mellitus. 1-palmitoyl lyso-PC was measured using electrospray ionization-liquid chromatography/mass spectrometry and Lp-PLA(2) by ELISA. Lyso-PC content in LDL was significantly higher in diabetic patients than in control healthy subjects. Lyso-PC content correlated significantly with Lp-PLA(2) levels (r=0.56, p<0.0001), and was significantly higher in patients with preproliferative or proliferative retinopathy and those with nephropathy than the control. Simvastatin treatment reduced serum Lp-PLA(2) and lyso-PC content in LDL. Our findings suggest that Lp-PLA(2) has the proatherogenic activity by contributing to the production of lyso-PC in circulating LDL. 相似文献