2.Multimorbidity of Allergic Diseases Is Associated With Functional Gastrointestinal Disorders in a Young Japanese Population
Yasunori YAMAMOTO ; Shinya FURUKAWA ; Teruki MIYAKE ; Junichi WATANABE ; Yukihiro NAKAMURA ; Yoshihiro TAGUCHI ; Tetsuya YAMAMOTO ; Aki KATO ; Katsunori KUSUMOTO ; Osamu YOSHIDA ; Eiji TAKESHITA ; Yoshio IKEDA ; Naofumi YAMAMOTO ; Yuka SAEKI ; Osamu YAMAGUCHI ; Yoichi HIASA
Journal of Neurogastroenterology and Motility 2024;30(2):229-235
		                        		
		                        			 Background/Aims:
		                        			Although certain allergic diseases have been reported to be associated with the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS), it is unclear whether the presence of multiple allergic diseases further increases the prevalence of FD and IBS.The aim of this study is to determine this issue in young people. 
		                        		
		                        			Methods:
		                        			A cohort of 8923 Japanese university students was enrolled and diagnoses of FD and IBS were confirmed using Rome III criteria.Allergic disorders diagnosed at medical institutions were obtained by means of a self-administered questionnaire. 
		                        		
		                        			Results:
		                        			The prevalence of FD, IBS, and their overlap was found to be 1.9%, 6.5%, and 1.1%, respectively. Pollen allergy was independently positively correlated with FD, IBS, and overlap of FD and IBS. Allergic rhinitis was positively linked to IBS. Drug allergy was positively associated with FD. The presence of multiple allergic diseases was positively correlated with FD and IBS (FD: adjusted OR for 2 allergic diseases: 1.95 [95% CI, 1.24-2.98], P for trend = 0.003; and IBS: adjusted OR for 1 allergic disease: 1.40 [95% CI, 1.15-1.69], 2 allergic diseases 1.47 [95% CI, 1.12-1.91], and 3 or more allergic diseases: 2.22 [95% CI, 1.45-3.28], P for trend = 0.001). Additionally, the concomitant existence of multiple allergic diseases was also demonstrated to have a trend that correlated with the overlap of FD and IBS (P for trend = 0.018). 
		                        		
		                        			Conclusion
		                        			Allergic disease multimorbidity is positively correlated with the prevalence of FD and IBS in a young population. 
		                        		
		                        		
		                        		
		                        	
3.Current Treatment Strategy for Superficial Nonampullary Duodenal Epithelial Tumors
Tetsuya SUWA ; Kohei TAKIZAWA ; Noboru KAWATA ; Masao YOSHIDA ; Yohei YABUUCHI ; Yoichi YAMAMOTO ; Hiroyuki ONO
Clinical Endoscopy 2022;55(1):15-21
		                        		
		                        			
		                        			 Endoscopic submucosal dissection (ESD) is the standard treatment method for esophageal, gastric, and colorectal cancers. However, it has not been standardized for duodenal lesions because of its high complication rates. Recently, minimally invasive and simple methods such as cold snare polypectomy and underwater endoscopic mucosal resection have been utilized more for superficial nonampullary duodenal epithelial tumors (SNADETs). Although the rate of complications associated with duodenal ESD has been gradually decreasing because of technical advancements, performing ESD for all SNADETs is unnecessary. As such, the appropriate treatment plan for SNADETs should be chosen according to the lesion type, patient condition, and endoscopist’s skill. 
		                        		
		                        		
		                        		
		                        	
4.A Case of Popliteal Endarterectomy in a Patient Post CABG
Kazunori HASHIMOTO ; Harunobu MATSUMOTO ; Takayuki YAMAMOTO ; Tetsuya SATO ; Satoshi ITO
Japanese Journal of Cardiovascular Surgery 2022;51(3):183-186
		                        		
		                        			
		                        			A 74-year-old man having a right refractory foot ulcer was referred to our hospital with a diagnosis of arteriosclerosis obliterans. Angiography of the lower extremities showed occlusive lesions in the middle popliteal artery and lower-leg arteries. Preoperative examination revealed decreased cardiac function and severe stenosis of the left and right coronary arteries. Therefore, we first performed coronary artery bypass grafting, followed by revascularization of the lower limbs at a later date. Owing to the lack of suitable autologous vein grafts, our procedure of choice was popliteal endarterectomy via a posterior approach with short saphenous vein angioplasty. The patient's foot ulcer healed completely following surgery. His postoperative course was uneventful, and he remained symptom-free during a 1-year follow-up.
		                        		
		                        		
		                        		
		                        	
6.Development of a competitive enzyme-linked immunosorbent assay for therapeutic drug monitoring of afatinib
Sogawa RINTARO ; Saita TETSUYA ; Yamamoto YUTA ; Kimura SAKIKO ; Narisawa YUTAKA ; Kimura SHINYA ; Shin MASASHI
Journal of Pharmaceutical Analysis 2019;9(1):49-54
		                        		
		                        			
		                        			Afatinib is an oral tyrosine kinase inhibitor (TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring (TDM) in clinical settings. This study sought to develop a simple and sensitive com-petitive enzyme-linked immunosorbent assay (ELISA) to quantify afatinib in plasma for routine phar-macokinetic applications. An anti-afatinib antibody was obtained using (S)-N-4-(3-chloro-4-fluor-ophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine (CTQD), which has the same sub-structure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods (Y = 0.976X – 0.207, r = 0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.
		                        		
		                        		
		                        		
		                        	
7.¹²³I-Labeled oxLDL Is Widely Distributed Throughout the Whole Body in Mice
Atushi NAKANO ; Hidekazu KAWASHIMA ; Yoshinori MIYAKE ; Tsutomu ZENIYA ; Akihide YAMAMOTO ; Kazuhiro KOSHINO ; Takashi TEMMA ; Tetsuya FUKUDA ; Yoshiko FUJITA ; Akemi KAKINO ; Shigehiko KANAYA ; Tatsuya SAWAMURA ; Hidehiro IIDA
Nuclear Medicine and Molecular Imaging 2018;52(2):144-153
		                        		
		                        			
		                        			PURPOSE: Oxidized low-density lipoprotein (oxLDL) plays a key role in endothelial dysfunction, vascular inflammation, and atherogenesis. The aim of this study was to assess blood clearance and in vivo kinetics of radiolabeled oxLDL in mice.METHODS: We synthesized ¹²³I-oxLDL by the iodine monochloride method, and performed an uptake study in CHO cells transfected with lectin-like oxLDL receptor-1 (LOX-1). In addition, we evaluated the consistency between the ¹²³I-oxLDL autoradiogram and the fluorescence image of DiI-oxLDL after intravenous injection for both spleen and liver. Whole-body dynamic planar images were acquired 10 min post injection of ¹²³I-oxLDL to generate regional time-activity curves (TACs) of the liver, heart, lungs, kidney, head, and abdomen. Regional radioactivity for those excised tissues as well as the bladder, stomach, gut, and thyroid were assessed using a gamma counter, yielding percent injected dose (%ID) and dose uptake ratio (DUR). The presence of ¹²³I-oxLDL in serum was assessed by radio-HPLC.RESULTS: The cellular uptakes of ¹²³I-oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of ¹²³I-oxLDL demonstrated extremely fast kinetics. The radioactivity uptake at 10 min postinjection was highest in the liver (40.8 ± 2.4% ID). Notably, radioactivity uptake was equivalent throughout the rest of the body (39.4 ± 2.7% ID). HPLC analysis revealed no remaining ¹²³I-oxLDL or its metabolites in the blood.CONCLUSION: ¹²³I-OxLDL was widely distributed not only in the liver, but also throughout the whole body, providing insight into the pathophysiological effects of oxLDL.
		                        		
		                        		
		                        		
		                        			Abdomen
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Atherosclerosis
		                        			;
		                        		
		                        			CHO Cells
		                        			;
		                        		
		                        			Chromatography, High Pressure Liquid
		                        			;
		                        		
		                        			Cricetinae
		                        			;
		                        		
		                        			Fluorescence
		                        			;
		                        		
		                        			Head Kidney
		                        			;
		                        		
		                        			Heart
		                        			;
		                        		
		                        			Inflammation
		                        			;
		                        		
		                        			Injections, Intravenous
		                        			;
		                        		
		                        			Iodine
		                        			;
		                        		
		                        			Kinetics
		                        			;
		                        		
		                        			Lipoproteins
		                        			;
		                        		
		                        			Liver
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			Methods
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Radioactivity
		                        			;
		                        		
		                        			Spleen
		                        			;
		                        		
		                        			Stomach
		                        			;
		                        		
		                        			Thyroid Gland
		                        			;
		                        		
		                        			Urinary Bladder
		                        			
		                        		
		                        	
8.¹²³I-Labeled oxLDL Is Widely Distributed Throughout the Whole Body in Mice
Atushi NAKANO ; Hidekazu KAWASHIMA ; Yoshinori MIYAKE ; Tsutomu ZENIYA ; Akihide YAMAMOTO ; Kazuhiro KOSHINO ; Takashi TEMMA ; Tetsuya FUKUDA ; Yoshiko FUJITA ; Akemi KAKINO ; Shigehiko KANAYA ; Tatsuya SAWAMURA ; Hidehiro IIDA
Nuclear Medicine and Molecular Imaging 2018;52(2):144-153
		                        		
		                        			 PURPOSE:
		                        			Oxidized low-density lipoprotein (oxLDL) plays a key role in endothelial dysfunction, vascular inflammation, and atherogenesis. The aim of this study was to assess blood clearance and in vivo kinetics of radiolabeled oxLDL in mice.
		                        		
		                        			METHODS:
		                        			We synthesized ¹²³I-oxLDL by the iodine monochloride method, and performed an uptake study in CHO cells transfected with lectin-like oxLDL receptor-1 (LOX-1). In addition, we evaluated the consistency between the ¹²³I-oxLDL autoradiogram and the fluorescence image of DiI-oxLDL after intravenous injection for both spleen and liver. Whole-body dynamic planar images were acquired 10 min post injection of ¹²³I-oxLDL to generate regional time-activity curves (TACs) of the liver, heart, lungs, kidney, head, and abdomen. Regional radioactivity for those excised tissues as well as the bladder, stomach, gut, and thyroid were assessed using a gamma counter, yielding percent injected dose (%ID) and dose uptake ratio (DUR). The presence of ¹²³I-oxLDL in serum was assessed by radio-HPLC.
		                        		
		                        			RESULTS:
		                        			The cellular uptakes of ¹²³I-oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of ¹²³I-oxLDL demonstrated extremely fast kinetics. The radioactivity uptake at 10 min postinjection was highest in the liver (40.8 ± 2.4% ID). Notably, radioactivity uptake was equivalent throughout the rest of the body (39.4 ± 2.7% ID). HPLC analysis revealed no remaining ¹²³I-oxLDL or its metabolites in the blood.
		                        		
		                        			CONCLUSION
		                        			¹²³I-OxLDL was widely distributed not only in the liver, but also throughout the whole body, providing insight into the pathophysiological effects of oxLDL. 
		                        		
		                        		
		                        		
		                        	
9.Quantitative determination of erlotinib in human serum using competitive enzyme-linked immunosorbent assay
Yamamoto YUTA ; Saita TETSUYA ; Yamamoto YUTARO ; Shin MASASHI
Journal of Pharmaceutical Analysis 2018;8(2):119-123
		                        		
		                        			
		                        			A selective and sensitive competitive enzyme-linked immunosorbent assay (ELISA) method was developed and validated for the quantification of erlotinib in 50μL of samples of human serum. Anti-erlotinib serum was obtained by immunizing mice with an antigen conjugated with bovine serum albumin and 3,4-bis(2-methoxyethoxy)benzoic acid using the N-succinimidyl ester method. Enzyme labeling of erlotinib with horseradish peroxidase was similarly performed using 3,4-bis(2-methoxyethoxy)benzoic acid. A simple competitive ELISA for erlotinib was developed using the principle of direct competition between erlotinib and the enzyme marker for anti-erlotinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Serum erlotinib concentrations lower than 40 ng/mL were reproducibly measurable using the ELISA. This ELISA was specific to erlotinib and showed very slight cross-reactivity (6.7%) with a major metabolite, O-desmethyl erlotinib. Using this assay, drug levels were easily measured in the blood of mice after oral administration of erlotinib at a single dose of 30 mg/kg. ELISA should be used as a valuable tool for therapeutic drug monitoring and in pharmacokinetic studies of erlotinib.
		                        		
		                        		
		                        		
		                        	
10.A Patient with Cat-scratch Disease Diagnosed by Detailed Medical History and Physical Examination
Syunsuke Kusano ; Tsuneaki Kenzaka ; Tetsuya Yamamoto ; Hozuka Akita
An Official Journal of the Japan Primary Care Association 2017;40(3):156-159
Cat-scratch disease occurs after a scratch from a cat infected with Bartonella henselae. We report a 64-year-old man with cat-scratch disease who had swollen lymph nodes. Consequently, metastasis of a malignant tumor was suspected as the most likely cause in the differential diagnosis. Therefore, the diagnosis was delayed and several diagnostic examinations were performed. Although diagnosis was difficult in this case, an accurate diagnosis was achieved by taking a detailed medical history, including questioning about pet ownership, and by carefully examining the lower limbs including the femoral region. These steps are important to diagnose cat-scratch disease.
            

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