A Case of Severe Hemorrhagic Cystitis Caused by Melphalan with Successful Bladder Preservation by Ligation of Bilateral Internal Iliac Arteries

Hemorrhagic cystitis is a disorder which causes bleeding from diffusely inflammatory bladder mucosa. Here we present a case of severe hemorrhagic cystitis caused by melphalan. A 70-year-old man with multiple myeloma was presented with suddenly commenced massive gross hematuria. During an attempt of transurethral coagulation of bladder mucosa, bladder perforation into peritoneal cavity was suspected, then open laparotomy was indicated. We isolated bilateral internal iliac arteries and ligated them in order to control continued bleeding. After that, bladder bleeding was suddenly diminished. Ligation of internal iliac arteries may be a choice in controlling massive bleeding from bladder with severe hemorrhagic cystitis when laparotomy was inevitable

Transient Occlusion of Bilateral Internal Iliac Arteries Facilitates Bloodless Operative Field in Subcapsular Prostatectomy

Transurethral resection of the prostate is the gold standard of surgical treatment for benign prostatic hyperplasia (BPH). Nevertheless, open subcapsular prostatectomy is still performed for large BPH. While enucleation of prostatic adenoma is being performed, unneglectable bleeding can occur and surgeons need to rush to remove adenomas, often using fingers and in a blinded fashion. The blood supply to the prostatic capsule and adenoma can be reduced to a marked extent in subcapsular prostatectomy if the bilateral internal iliac arteries are transiently occluded. Thus, a bloodless operative field is reasonably acquired during enucleation of adenoma, which would, otherwise, be a cause for concern to surgeons due to bleeding. It is not always applicable, but it could be an option if the estimated volume of BPH is more than 100 mL. In two cases, bilateral internal iliac arteries were occluded with Bulldog clamps, and then adenomas of 159 and 97 g were enucleated

Surgical Castration in Hormone-Refractory Metastatic Prostate Cancer Patients Can Be an Alternative for Medical Castration

Background. Most patients with metastatic prostate cancer are endocrinologically treated with LHRH agonist, but finally castration-refractory and hormone-refractory cancers occur. Serum testosterone levels get low to “the castration level” by LHRH agonists but may not get low enough against castration-refractory prostate cancer. Methods. As case series, twelve patients suffering from hormone-refractory prostate cancer continuously on LHRH agonist underwent surgical castration. Additionally, one hundred and thirty-nine prostate cancer patients on LHRH agonist or surgical castration were tested for serum total testosterone levels. Results. Surgical castration caused decrease in serum PSA in one out of 12 hormone-refractory prostate cancer patients with PSA reduction rate 74%. Serum total testosterone levels were below the sensitivity threshold (0.05 ng/mL) in 40 of 89 (44.9%) medically castrated patients and 33 of 50 (66.0%) surgically castrated patients (P = .20). Conclusion. Even hormone-refractory prostate cancer patients are candidates for surgical castration because of endocrinological, oncological, and economical reasons

Efficacy and safety of nintedanib in Japanese patients with progressive fibrosing interstitial lung diseases : Subgroup analysis of the randomised, double-blind, placebo-controlled, phase 3 INBUILD trial

Background: The efficacy of nintedanib in progressive fibrosing interstitial lung diseases (ILDs) was demonstrated in the randomised, double-blind, placebo-controlled INBUILD trial. This subgroup analysis evaluated the efficacy and safety of nintedanib in the Japanese population. Methods: Patients with progressive fibrosing ILDs (evaluated by physicians within 24 months of screening) were randomised (1:1) to twice-daily 150-mg nintedanib or placebo; treatment continued until the last patient completed 52 weeks. The primary endpoint was the annual rate of decline in forced vital capacity (FVC) over 52 weeks. Time-to-first acute ILD exacerbation or death and time-to-death up until the last patient had completed the week 52 visit were evaluated. This subgroup analysis included 108 Japanese patients. Results: The adjusted annual rates of FVC decline (mL/year) over 52 weeks for Japanese patients were −148.31 (nintedanib) and −240.36 (placebo), adjusted difference: 92.05 (95% CI: −10.69–194.80) and for non-Japanese patients were −67.41 (nintedanib) and −177.65 (placebo), adjusted difference: 110.24 (95% CI: 64.97–155.52). No heterogeneity in treatment effect between Japanese and non-Japanese subgroups was observed (treatment-by-subgroup interaction, p = 0.75). The risks of “acute exacerbation or death” (hazard ratio, 0.30 [95% CI: 0.10–0.91]) and mortality (hazard ratio, 0.54 [95% CI: 0.14–2.11]) in Japanese patients were numerically lower for nintedanib than placebo. There were no new or unexpected safety findings. Conclusions: In Japanese patients, nintedanib slowed ILD progression, evidenced by a reduction in the annual rate of decline in FVC vs placebo. The efficacy and safety of nintedanib in Japanese patients were consistent with the overall INBUILD population

A flexible representation of omic knowledge for thorough analysis of microarray data

BACKGROUND: In order to understand microarray data reasonably in the context of other existing biological knowledge, it is necessary to conduct a thorough examination of the data utilizing every aspect of available omic knowledge libraries. So far, a number of bioinformatics tools have been developed. However, each of them is restricted to deal with one type of omic knowledge, e.g., pathways, interactions or gene ontology. Now that the varieties of omic knowledge are expanding, analysis tools need a way to deal with any type of omic knowledge. Hence, we have designed the Omic Space Markup Language (OSML) that can represent a wide range of omic knowledge, and also, we have developed a tool named GSCope3, which can statistically analyze microarray data in comparison with the OSML-formatted omic knowledge data. RESULTS: In order to test the applicability of OSML to represent a variety of omic knowledge specifically useful for analysis of Arabidopsis thaliana microarray data, we have constructed a Biological Knowledge Library (BiKLi) by converting eight different types of omic knowledge into OSML-formatted datasets. We applied GSCope3 and BiKLi to previously reported A. thaliana microarray data, so as to extract any additional insights from the data. As a result, we have discovered a new insight that lignin formation resists drought stress and activates transcription of many water channel genes to oppose drought stress; and most of the 20S proteasome subunit genes show similar expression profiles under drought stress. In addition to this novel discovery, similar findings previously reported were also quickly confirmed using GSCope3 and BiKLi. CONCLUSION: GSCope3 can statistically analyze microarray data in the context of any OSML-represented omic knowledge. OSML is not restricted to a specific data type structure, but it can represent a wide range of omic knowledge. It allows us to convert new types of omic knowledge into datasets that can be used for microarray data analysis with GSCope3. In addition to BiKLi, by collecting various types of omic knowledge as OSML libraries, it becomes possible for us to conduct detailed thorough analysis from various biological viewpoints. GSCope3 and BiKLi are available for academic users at our web site

Nationwide retrospective observational study of idiopathic dendriform pulmonary ossification : clinical features with a progressive phenotype

Background: Diffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO. Methods: We conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO. Results: Twenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22-56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1s). Two cases with rapid decline of 10% /year in %FVC predicted were observed. )) at diagnosis. Nearly 80% of the subjects wereasymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1s). Two cases with rapid decline of 10% /year in %FVC predicted were observed. Conclusions: IDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO

Validation of Pyrosequencing for the Analysis of KRAS Mutations in Colorectal Cancer

The use of antibodies against epidermal growth factor receptor( EGFR) in conjunction with conventionalchemotherapy for metastatic colorectal cancer (CRC) in patients with KRAS wild-type tumors has beenproven to be efficacious. Recently, KRAS testing prior to anti-EGFR therapy has become mandatory formetastatic CRC patients. Although newly developed pyrosequencing is expected to be one of the highthroughput procedures detecting such mutations, the accuracy of the procedure has not been well evaluated.In the present study, we aimed to validate the accuracy, especially the potential for a false-negative result,in detecting KRAS mutations by pyrosequencing using cultured tumor cells. DNA extracted from cultured&igrave;NOZ&icirc; gallbladder cancer cells( known to contain KRAS mutation G12V) at concentrations of 1%, 5%, 10%, and 25%, as well as 2 DNA samples extracted from a resected CRC specimen( known to contain anotherKRAS mutation, G12C) at concentrations of 5% and 25%, were prepared. We analyzed KRAS mutationalstatus and nonexistent and/or nonfunctional mutations of these 6 samples using pyrosequencing. TheKRAS mutation detection rates in the 4 NOZ samples( 1%, 5%, 10%, and 25%) were 0.37%, 2.79%, 5.28%,and 13.85%, respectively. Some artifacts of KRAS mutations unlikely to be present were detected in 1%samples of NOZ at a rate similar to that of the G12V mutation( G12C, 0.29%;G13C, 0.42%). Although theKRAS mutation G12C was detected at rates of 1.26% and 6.49% in samples with 5% and 25% DNA extractedfrom resected CRC specimen, respectively, no other type of KRAS mutation was detected in suchsamples. Pyrosequencing could not detect KRAS mutations correctly in the sample containing 1% DNA.This might cause false negatives. A sample mutated DNA concentration of at least 5% was necessary forprecise analyses by this procedure

Identification of Carnitine Transporter CT1 Binding Protein Lin-7 in Nervous System

_L-Carnitine is an essential component of mitochondrial fatty acid b-oxidation in the muscle and may control the acetyl moiety levels in the brain for acetylcholine synthesis. Carnitine transporter 1(CT1)is the high affinity _L-carnitine transporter whose localization was observed in the kidney, testis, liver, skeletal muscle and brain. To clarify the molecular mechanism of carnitine transport, we sought to find the interacting protein that may be related to the transport function of CT1. Using the intracellular C-terminal region of rat CT1 containing PDZ(PSD95/DLG/ZO-1)motif as bait, we performed the yeast two-hybrid screening against rat brain cDNA library. Thirty two positive clones were obtained from the 2.7×10^7 clones screened. One of them was PDZ domain-containing protein Lin-7. We found that Lin-7 interacts specifically with C-termini of CT1:deletion and mutation of the CT1 C-terminal PDZ-motif abolished the interaction with Lin-7 in the yeast two-hybrid assay. In addition, a PDZ domain within Lin-7 associates with the CT1 C-terminal. The association of CT1 with Lin-7 enhanced _L-carnitine transport activities in HEK293 cells although there is no statistical significance. Coexpression of Lin-7 and CT1 is identified in motor neurons of the spinal cord ventral horn together with Lin-2, a binding partner of Lin-7 known to assemble proteins involved in synaptic vesicle exocytosis and synaptic junctions. Therefore, Lin-7 interacts with CT1 and may regulate their subcellular distribution or function in central nervous system

ヒト ジンゾウ ニョウサン トランス ポーター URAT 1 ト スイヨウ セイ ヨード ケイ ゾウエイザイ IODIPAMIDE ノ ソウゴ サヨウ

降圧薬などいくつかの薬剤は本来の薬理作用とは別に尿酸降下作用を持つものがあり,水溶性ヨード系造影剤もその一つでiodipamideやdiatrizoateでの尿酸排泄亢進が報告されていた.長らく不明のままであった腎尿酸輸送機構の分子実体は2002年の腎尿細管尿酸トランスポーターURAT1(Urate Transporter 1)の分子同定によりその理解が飛躍的に進んだ.本研究ではURAT1と水溶性造影剤のiodipamideおよびdiatrizoateの相互作用を検討することで,その尿酸排泄促進作用の分子機序の解明を目的とする.URAT1の尿酸輸送活性の測定にはURAT1安定発現HEK293細胞(HEK-URAT1)細胞を用いた.IodipamideはHEK-URAT1細胞でのRI標識尿酸取込みを著明に阻害した(IC_:1.19±0.08?μM)のに対し,diatrizoateは1?mMまでの範囲では50%以上の阻害作用を示さなかった.1?mMまでのiodipamideはHEK-URAT1細胞の生存率に影響を与えなかった.IodipamideによるURAT1媒介尿酸輸送への阻害作用のキネティクス解析の結果,その阻害は競合阻害であり,阻害定数Ki値は11.03?μMであった.以上より,iodipamideは尿酸トランスポーターURAT1と相互作用をすることを初めて確認できた.このことからiodipamideは細胞外からURAT1の尿酸結合部位に結合し,競合して阻害を行うことで,腎尿細管の経上皮性尿酸再吸収を抑制し,ひいては血清尿酸値を低下させるものと考えられた.Drug-induced hypouricemia has been found in several drugs such as probenecid, benzbromarone and angiotensin II receptor blocker(ARB)losartan. Xray contrast agents such as iodipamide and diatrizoate, used for the intravenous cholangiography and excretory urography, were reported to have uricosuric effct beside their original action. After the molecular identification of renal apical urate transporter URAT1 as an entrance of urate into the epithelial cells of proximal tubules, this protein is thought to be major determinant for renal reabsorption of urate that affect the blood urate levels in human. The purpose of this study is to examine whether iodipamide and diatrizoate act on URAT 1 . In URAT 1 -stably expressing HEK293(HEK-URAT1)cells, iodipamide inhibited [^C] urate uptake dose-dependently(IC_ , 1.19±0.08 μM), while diatrizoate did not. Up to the concentration of 1 mM, iodipamide incubation for 24 hr did not affect the viability of HEK293-URAT1 cells. Lineweaver-Burk plot of the kinetic analysis by URAT1-mediated urate uptake with or without iodipamide indicated that its interaction occurs in a competitive manner(Ki:11.03 μM). These results suggest that uricosuric effect of iodipamide can be explained by the interaction of iodipamide with urate-binding site of URAT1, and the inhibition of urate reabsorption from extracellular side by iodipamide causes uricosuria leading to induce hypouricemia