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Cell-to-cell transmission of α-synuclein (α-syn) pathology underlies the spread of neurodegeneration in Parkinson's disease. α-Syn secretion is an important factor in the transmission of α-syn pathology. However, it is unclear how α-syn secretion is therapeutically modulated. Here, we investigated effects of monoamine oxidase (MAO)-B inhibitor selegiline on α-syn secretion. Treatment with selegiline promoted α-syn secretion in mouse primary cortical neuron cultures, and this increase was kept under glial cell-eliminated condition by Ara-C. Selegiline-induced α-syn secretion was blocked by cytosolic Ca 2+ chelator BAPTA-AM in primary neurons. Selegiline-induced α-syn secretion was retained in MAOA siRNA knockdown, whereas it was abrogated by ATG5 knockdown in SH-SY5Y cells. Selegiline increased LC3-II generation with a reduction in intracellular p62/SQSTM1 levels in primary neurons. The increase in LC3-II generation was blocked by co-treatment with BAPTA-AM in primary neurons. Additionally, fractionation experiments showed that selegiline-induced α-syn secretion occurred in non-extracellular vesicle fractions of primary neurons and SH-SY5Y cells. Collectively, these findings show that selegiline promotes neuronal autophagy involving secretion of non-exosomal α-syn via a change of cytosolic Ca 2+ levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis., Methods: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019., Results: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis., Conclusion: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents., Competing Interests: Declaration of Competing interest Tokimatsu I. received scholarship donations from Shionogi Pharmaceuticals, Inc. and Daiichi Sankyo Co. Ltd. Ukimura A. received scholarship donations from Shionogi Pharmaceuticals, Inc. Hiroshige Mikamo received speaker honoraria from MSD K.K., FUJIFILM Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Shionogi & Co., Ltd. Japan, Kowa Co. Ltd., Gilead Sciences K.K., GSK Group of Companies, Saraya Co. Ltd., Tsumura & Co. Japan, Nippon Becton Dickinson Company, Ltd., and FUKOKU Co., Ltd., grant supports from Asai Kasei Pharma Co., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., and FUKOKU Co., Ltd. Mitsutake K, Shinya N, Seki M, Ohara T, Uemura K, Fukunaga M, Sakai J, Nagao M, Sata M, Hamada Y, Kawasuji H, Yamamoto Y, Nakamatsu M, Koizumi Y, Aoyagi T, Sawai T, Tanaka T, Izumikawa K, Takayama Y, Nakamura K, Kanemitsu K, Nakajima K, and Akine D have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: No comprehensive analysis of the pulmonary sequelae of coronavirus disease 2019 (COVID-19) in Japan based on respiratory function tests and chest computed tomography (CT) has been reported. We evaluated post-COVID-19 conditions, especially focusing on pulmonary sequelae assessed by pulmonary function tests and chest CT., Methods: For this prospective cohort study, we enrolled 1069 patients who presented pneumonia at the time of admission in 55 hospitals from February 2020 to September 2021. Disease severity was classified as moderateⅠ, moderate II, and severe, defined primarily according to the degree of respiratory failure. The data on post-COVID-19 conditions over 12 months, pulmonary function, and chest CT findings at 3 months were evaluated in this study. Additionally, the impact of COVID-19 severity on pulmonary sequelae, such as impaired diffusion capacity, restrictive pattern, and CT abnormalities, was also evaluated., Results: The most frequently reported post-COVID-19 conditions at 3 months after COVID-19 were muscle weakness, dyspnea, and fatigue (48.4%, 29.0%, and 24.7%, respectively). The frequency of symptoms gradually decreased over subsequent months. In pulmonary function tests at 3 months, the incidence of impaired diffusion capacity and restrictive pattern increased depending on disease severity. There also were differences in the presence of chest CT abnormalities at the 3 months, which was markedly correlated with the severity., Conclusion: We reported a comprehensive analysis of post-COVID-19 condition, pulmonary function, and chest CT abnormalities in Japanese patients with COVID-19. The findings of this study will serve as valuable reference data for future post-COVID-19 condition research in Japan., Competing Interests: Declaration of Competing interest The authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP., Methods: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis., Result: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed., Conclusion: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications., Competing Interests: Declaration of competing interest Hiroshi Mukae received lecture honoraria and research grants from KYORIN Pharmaceutical Co., Ltd. Outside of the submitted work., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Infective endocarditis (IE) caused by MRSA (methicillin-resistant Staphylococcus aureus) is associated with a high mortality rate. This study aimed to elucidate the characteristics of patients with MRSA-IE in Japan and identify the factors associated with prognosis., Methods: This retrospective study included patients with a confirmed diagnosis of IE caused by MRSA, between January 2015 and April 2019., Results: A total of 65 patients from 19 centers were included, with a mean age of 67 years and 26 % were female. Fifty percent of the patients with IE were had nosocomial infections and 25 % had prosthetic valve involvement. The most common comorbidities were hemodialysis (20 %) and diabetes (20 %). Congestive heart failure was present in 86 % of patients (NYHA class I, II: 48 %; III, IV: 38 %). The 30-day and in-hospital mortality rates were 29 % and 46 %, respectively. Multi-organ failure was the primary cause of death, accounting for 43 % of all causes of death. Prognostic factors for in-hospital mortality were age, disseminated intravascular coagulation, daptomycin and/or linezolid as initial antibiotic therapy, and surgery. Surgical treatment was associated with a lower mortality rate (odds ratio [OR], 0.026; 95 % confidence interval [CI], 0.002-0.382; p = 0.008 for 30-day mortality and OR, 0.130; 95 % CI; 0.029-0.584; p = 0.008 for in-hospital mortality)., Conclusion: Mortality due to MRSA-IE remains high. Surgical treatment is a significant prognostic predictor of MRSA-IE., Competing Interests: Declaration of competing interest Tokimatsu I. received scholarship donations from Shionogi Pharmaceuticals, Inc. and Daiichi Sankyo Co., Ltd. Ukimura A. received scholarship donations from Shionogi Pharmaceuticals Inc. Hiroshige Mikamo received speaker honoraria from MSD K.K., FUJIFILM Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Shionogi & Co., Japan. Ltd., Kowa Co. Ltd., Gilead Sciences K.K., the GSK Group of Companies, Saraya Co. Ltd., and Tsumura and Co. Japan, Nippon Becton Dickinson Company, Ltd., and FUKOKU Co., Ltd., and grant support from Asai Kasei Pharma Co., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., and FUKOKU Co., Ltd. Mitsutake K, Shinya N, Seki M, Ohara T, Uemura K, Fukunaga M, Sakai J, Nagao M, Sata M, Hamada Y, Kawasuji H, Yamamoto Y, Nakamatsu M, Koizumi Y, Aoyagi T, Sawai T, Tanaka T, Izumikawa K, Takayama Y, Nakamura K, Kanemitsu K, Nakajima K, and Akine D have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Although the efficacy of lung cancer treatment has improved, it is dependent on a reliable diagnosis via bronchoscopy. Transbronchial biopsy using ultrathin bronchoscopy can help detect small peripheral pulmonary lesions (PPLs), with a high diagnostic yield. However, the diagnosis rate using forceps biopsy when the radial endobronchial ultrasonography (rEBUS) probe is adjacent to a lesion tends to be low. Transbronchial needle aspiration (TBNA) may improve the diagnostic yield from adjacent lesions. Recently, PeriView FLEX, a new TBNA needle that can be inserted into ultrathin bronchoscopes, has become available. We examined whether TBNA with PeriView FLEX and forceps biopsy improved adjacent lesion diagnosis when using ultrathin bronchoscopes., Methods: We retrospectively examined 51 consecutive patients who underwent TBNA and forceps biopsy using ultrathin bronchoscopes under rEBUS for small PPLs at the Hakodate Goryoukaku Hospital between November 2019 and August 2020. The histological diagnosis rate using TBNA and forceps biopsy, TBNA alone, or forceps biopsy alone was compared between cases where the rEBUS probe was "Within" and "Adjacent To" the lesions., Results: The diagnosis rate using TBNA and forceps biopsy was 86.3% (95.7% vs. 78.6%; p = 0.08) for all lesions (Within cases vs. Adjacent To cases). The corresponding rate using TBNA alone was 68.6% (69.6% vs. 67.9%; p = 0.57), and that using forceps biopsy alone was 72.5% (91.3% vs. 57.1%; p = 0.0067)., Conclusions: Forceps biopsy with TBNA during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when lesions were adjacent to the rEBUS probe., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary for confirming a diagnosis of Coronavirus disease 2019 (COVID-19). Here we present a COVID-19 case of an elderly woman whose SARS-CoV-2 PCR tests showed false negative repeatedly by evaluating with different sampling sites and procedures. Nasopharyngeal swabs, suctioned sputum, and tongue swabs were collected for SARS-CoV-2-PCR. As for tongue swabs, we compared between two different sample conditions; one obtained with dry condition and the other obtained with moistened condition inside the oral cavity. SARS-CoV-2-PCR showed positive for an extended period with suctioned sputum samples compared with nasopharyngeal swabs and tongue swabs. No SARS-CoV-2 from a nasopharyngeal swab sample obtained on day 46 after symptoms onset was isolated despite high viral load (183740.5 copies/5μL). An adequate production of neutralizing antibody in a serum sample on day 46 was also confirmed. The number of RNA copies of the tongue swab samples was higher with moistened condition than with dry condition. The present case suggests that the difference of sampling site or sample condition can affect PCR results. High loads viral RNA detection does not always correlate with infectivity., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Frasier syndrome (FS) is a rare inherited kidney disease caused by intron 9 splicing variants of WT1 . For wild-type WT1 , 2 active splice donor sites in intron 9 cause a mixture of 2 essential transcripts (with or without lysine-threonine-serine [+/KTS or -KTS]), and imbalance of the +KTS/-KTS ratio results in the development of FS. To date, 6 causative intron 9 variants have been identified; however, detailed transcript analysis has not yet been conducted and the genotype-phenotype correlation also remains to be elucidated., Methods: We conducted an in vitro minigene splicing assay for 6 reported causative variants and in vivo RNA sequencing to determine the +KTS/-KTS ratio using patients' samples. We also performed a systematic review of reported FS cases with a description of the renal phenotype., Results: The in vitro assay revealed that although all mutant alleles produced -KTS transcripts only, the wild-type allele produced both +KTS and -KTS transcripts at a 1:1 ratio. In vivo RNA sequencing showed that patients' samples with all heterozygous variants produced similar ratios of +KTS to -KTS (1:3.2-1:3.5) and wild-type kidney showed almost a 1:1 ratio (1:0.85). A systematic review of 126 cases clarified that the median age of developing ESKD was 16 years in all FS patients, and there were no statistically significant differences between the genotypes or sex chromosome karyotypes in terms of the renal survival period., Conclusion: Our study suggested no differences in splicing pattern or renal survival period among reported intron 9 variants causative of FS., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests exists commercially; however, their performance using clinical samples is limited. Although insufficient to detect SARS-CoV-2 in the early phase of infection, antibody assays can be of great use for surveillance studies or for some coronavirus disease 2019 (COVID-19) patients presenting late to the hospital., Methods: This study evaluated the sensitivity and specificity of four commercial SARS-CoV-2 lateral flow antibody tests using 213 serum specimens from 90 PCR-positive confirmed COVID-19 patients. Of 59 negative control sera, 50 were obtained from patients with other respiratory infectious diseases before COVID-19 pandemic began while nine were from patients infected with other respiratory viruses, including two seasonal coronaviruses., Results: The varied sensitivities for the four commercial kits were 70.9%, 65.3%, 45.1%, and 65.7% for BioMedomics, Autobio Diagnostics, Genbody, and KURABO, respectively, between sick days 1 and 155 in COVID-19 patients. The sensitivities of the four tests gradually increased over time after infection before sick day 5 (15.0%, 12.5%, 15.0%, and 20.0%); from sick day 11-15 (95.7%, 87.2%, 53.2%, and 89.4%); and after sick day 20 (100%, 100%, 68.6%, and 96.1%), respectively. For severe illness, the sensitivities were quite high in the late phase after sick day 15. The specificities were over 96% for all four tests. No cross-reaction due to other pathogens, including seasonal coronaviruses, was observed., Conclusions: Our results demonstrated the large differences in the antibody test performances. This ought to be considered when performing surveillance analysis., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: In advanced lung cancer, precision medicine requires repeated biopsies via bronchoscopy at therapy change. Since bronchoscopies are often stressful for patients, sedation using both fentanyl and midazolam is recommended in Europe and America. In Japan, bronchoscopies are generally orally performed under midazolam and oropharyngeal anesthesia. Nasal intubation creates a physiological route to the trachea, causing less irritation to the pharynx than intubation via the oral cavity; however, the necessity of oropharyngeal anesthesia remains unclear. We aimed to compare the safety, patient discomfort, and diagnostic rates for oropharyngeal anesthesia and sedation with pethidine and midazolam (Group A) and sedation with midazolam and fentanyl without oropharyngeal anesthesia (Group B) for ultrathin bronchoscopy of peripheral pulmonary lesions (PPLs) via nasal intubation., Methods: We retrospectively reviewed 74 consecutive potential lung cancer patients who underwent ultrathin bronchoscopies at the Hakodate Goryoukaku Hospital between July 2019 and June 2020. We reviewed the following: diagnostic rates; cumulative doses of lidocaine, midazolam, and fentanyl; hemodynamic changes; procedural complications in both groups. Pharyngeal anesthesia in group A was administered by spraying 2% (w/v) lidocaine into the pharynx. The chi-squared test was used for statistical analyses., Results: There were no significant changes in hemodynamic parameters and complications. The mean level of discomfort for bronchoscopic examinations was significantly lower in Group B (2.39 vs. 1.64; P = 0.014), with no significant inter-group difference in the diagnostic yields for PPLs (63.0% vs. 71.4%; P = 0.46)., Conclusions: Our findings indicate the advantages of sedation with fentanyl and midazolam without oropharyngeal anesthesia for ultrathin bronchoscopy through nasal intubation., Competing Interests: Conflict of interests The authors declare no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to β-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC 90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with β-lactamase inhibitor showed low MIC 90 values., Competing Interests: Declaration of competing interest Tetsuya Matsumoto received speaker honoraria from MSD K.K., and Pfizer Japan Inc., Hiroshi Kiyota received scholarship donations from Taisho Toyama Pharmaceutical Co., Ltd., Fujifilm Toyama Chemical Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., Taiho Pharmaceutical Co., Ltd., and Sanofi K.K., Kazuhiro Tateda received speaker honoraria from Pfizer Japan Inc., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Meiji Seika Pharma Co., Ltd., and Taisho Toyama Pharmaceutical Co., Ltd., and grant support from Hitachi, Ltd., Nissui Pharmaceutical Co., Ltd., BD Japan Co., Ltd., Denka Co., Ltd., Kaneka Co., and Shimadzu Co., received scholarship donations from Fujifilm Toyama Chemical Co., Ltd., Meiji Seika Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Sumitomo Dainippon Pharma Co., Ltd., Shionogi & Co., Ltd., and Asahi Kasei Pharma Co., Hiromitsu Kishimoto received speaker honoraria from Daiichi Sankyo Co., Ltd., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: For the precise management of advanced lung cancers, bronchoscopy with a high diagnostic yield and abundant tumor specimens are required. In recent years, new devices and techniques have been rapidly developed, including the endobronchial ultrasound (EBUS) using a guide sheath, virtual bronchoscopic navigation (VBN), and ultra-thin bronchoscope (UTB), for the diagnosis of peripheral pulmonary lesions (PPLs). These techniques increase the diagnostic yield for PPL, thus requiring fewer biopsy specimens. VBN is generally not available at the city hospitals in Japan. In this study, using fluoroscopy without VBN, we studied whether the histologic diagnostic yield of radial EBUS for PPLs would be higher using a UTB (without guide sheath) or conventional bronchoscope (CB) (with guide sheath)., Methods: We retrospectively reviewed consecutive patients with suspected lung cancer who underwent bronchoscopy at the Hakodate Goryoukaku Hospital from April 2017 to March 2019. We analyzed 168 patients-102 using UTB and 66 using CB., Results: The diagnostic yields for PPL were significantly higher in the UTB group than in the CB group (74.5% vs. 59.1%; P = 0.04). The median examination time was significantly longer in the UTB group than in the CB group (24 vs. 20 min; P = 0.01). There were no statistically significant differences in the complication rate between the UTB and CB groups (3.9% vs. 3.0%; P = 0.69)., Conclusions: UTB had a significantly higher tissue diagnostic yield than CB, without the use of VBN., (Copyright © 2020. Published by Elsevier B.V.)

Oral antibiotic therapy for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves an aminopenicillin with clavulanic acid, a macrolide, or a quinolone. To date, however, the clinical efficacy and safety of the oral cephalosporin cefditoren pivoxil has not been evaluated in Japanese patients with acute exacerbations of COPD. We conducted a prospective, multicenter, single arm, interventional study from January 2013 to March 2017 to determine the efficacy and safety of oral administration of 200 mg cefditoren pivoxil three times daily for 7 days in a cohort of 29 eligible patients from 15 hospitals. The mean age (SD) of participants was 73.1 (8.1) years and 28 had a smoking history (the mean [SD] of smoking index, 1426.7 [931.7]). The primary efficacy endpoint was clinical response (cure rate) at test of cure, which was set at 5-10 days after treatment ceased. Of the 23 patients finally analyzed, cure was achieved in 15 (65.2%), while 8 (34.8%) remained uncured. Previous experience of acute exacerbations significantly affected the cure rate: none of the three patients who had at least two prior exacerbations were cured, while 15 of the 20 patients with one or fewer prior exacerbations were cured (p = 0.032). The microbiological eradication rate was 88.9% at test of cure. During treatment, mild pneumonia was reported as an adverse event in one patient (3.4%) but resolved within 10 days of onset. We conclude that cefditoren pivoxil represents a viable alternative for antibiotic therapy in patients with few prior exacerbations., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Study Objective: To examine postoperative sore throat resulting from tracheal intubation stylet removal., Design: Prospective cohort study., Setting: Operating rooms and hospital ward., Patients: A total of 50 American Society of Anesthesiologists physical status 1 and 2 patients who underwent elective abdominal and/or orthopedic surgery under general anesthesia., Interventions: Patients were allocated to 2 groups: those who developed sore throat postoperatively (ST group) and those who did not (NST group). Comparative analysis of these 2 groups was performed to identify risk factors of the development of sore throat., Measurements: The extraction force during stylet removal was measured using a force measuring device. Postoperative sore throat was assessed by an anesthesiologist., Main Results: Nine patients (18%) complained of postoperative sore throat. Increased extraction force (P=.0054; odds ratio, 1.84; 95% confidence interval, 1.20-2.84) was the only significant risk factor for the development of postoperative sore throat. An extraction force of >10.3N was determined as a cutoff for developing postoperative sore throat., Conclusion: Postoperative sore throat was significantly related to increased extraction force during stylet removal., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Total paraplegia after epidural or spinal anesthesia is extremely rare. We herein report a case of total paraplegia caused by a giant intradural herniation of a lumbar disk at the L3-L4 level after total hip arthroplasty for coxarthrosis. The patient had no preoperative neurologic abnormalities. Intraoperative anesthetic management involved combined spinal-epidural anesthesia at the L3-L4 level with continuous intravenous propofol administration. Postoperatively, the patient complained of numbness and total paraplegia of the lower extremities. Magnetic resonance imaging showed a giant herniation of a lumbar disk compressing the spinal cord at the L3-L4 level. The intradural herniation was surgically treated, and the patient's symptoms completely resolved., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Prognostic influences of hepatic transection by an anterior approach using the liver hanging maneuver (LHM) has not been fully clarified., Methods: We examined 233 patients who underwent major hepatectomy with the LHM (n = 75; hepatocellular carcinoma (HCC) in 35, colorectal liver metastasis (CLM) in 10, intrahepatic cholangiocarcinoma (ICC) in 14 and perihilar bile duct carcinoma (BDC) in 16) or without it (n = 158; HCC in 78, CLM in 21, ICC in 31 and BDC in 28)., Results: In HCC patients, cancer-positive margin rate, blood loss, transection time and prevalence of posthepatectomy ascites in the LHM group were significantly lower than those in the non-LHM group (p < 0.05). In CLM, transection time in the LHM group was significantly lower than that in the non-LHM group (p < 0.05). In BDC patients, amount of blood loss, transection time and prevalence of ascites in the LHM group were significantly lower than those in the non-LHM group (p < 0.05). In CLM patients, tumor recurrence rate in the non-LHM group was significantly higher than that in the LHM group and disease-free survival in the LHM group was significantly better than that in the non-LHM group in CLM patients and, however, this difference was not observed in a large CLM exceeding 5 cm. However, significant differences of posthepatectomy disease-free and overall survivals were not observed in HCC, ICC and BDC patients., Conclusions: Although advantages of LHM improving surgical records in major anatomical liver resections were clarified, oncological advantages in the long-term survival of LHM was still uncertain in the hepatobiliary malignancies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Rapamycin has been reported to inhibit mesenchymal cell proliferation in a murine model of pulmonary fibrosis. In the present study, we examined the effects of rapamycin on vascular remodeling including intraluminal myofibroblast proliferation in a murine model of allergic vasculitis with eosinophil infiltration., Methods: C57BL/6 mice were sensitized with ovalbumin (OVA) and alum. The positive controls were exposed to aerosolized OVA daily for 7 days. The other group of mice was administered with rapamycin (1mg/kg) intraperitoneally, in parallel with daily exposure to aerosolized OVA for 7 days. On the 3rd and 7th day, bronchoalveolar lavage (BAL) was performed and the lungs were excised for pathological analysis. Cell differentials were determined and concentrations of IL-4, IL-5, IL-13 and TGF-β in the BAL fluid (BALF) were measured. Semi-quantitative analysis of pathological changes in the pulmonary arteries was evaluated according to the severity of vasculitis., Results: The number of eosinophils in BALF was reduced significantly in the mice treated with rapamycin compared to the positive control. There was a significant decrease in the TGF-β concentration of the BALF in the rapamycin-treated group compared to that of the positive control. The pathological scores were reduced significantly in the rapamycin-treated group compared to the positive control group. Intraluminal myofibroblasts in pulmonary arteries were reduced dramatically in the rapamycin-treated group compared to the positive control group., Conclusions: Rapamycin suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration through reducing eosinophil infiltration and TGF-β production in the lung and inhibition against biological action of TGF-β.

Nocardia spp. has not been reported previously as a cause of post-influenza pneumonia. Here we present a first case of post-influenza bacterial pneumonia due to Nocardia farcinica. Initial reason for hospitalization of the 90 year old female patient was a pneumonia with the symptoms of fever and productive cough. A rapid test for influenza antigen was positive for influenza A virus. Treatment with Zanamivir and piperacillin was initiated. However, after 1 week of treatment, the infiltration shadows on chest X-ray had worsened. Because the expectorated sputum collected on admission for culture was found to be positive for Nocardia spp., piperacillin was replaced with trimethoprim/sulfamethoxazole, and a chest X-ray showed some improvement. Although pulmonary nocardiosis with co-infection with influenza A is extremely rare, clinicians should be alert to the possibility., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The novel biological agent recombinant human thrombomodulin (rhTM) has been used clinically in Japan to treat disseminated intravascular coagulation (DIC) since 2008. Previous studies have shown the efficacy of rhTM versus heparin therapy or non-rhTM therapy. We retrospectively evaluated and compared the efficacies of rhTM and gabexate mesilate (GM) in patients diagnosed with sepsis-induced DIC. From September 2010 to October 2012, patients with sepsis-induced DIC who were treated with rhTM (n = 13) or GM (n = 10) at Nagasaki Municipal Hospital were extracted. Patients receiving other anticoagulants in combination were excluded. Clinical information, laboratory data, Sequential Organ Failure Assessment (SOFA) scores, and DIC scores were obtained from the medical records. Mortality at days 7 and 30 after DIC diagnosis and changes in laboratory data and SOFA scores from days 1-7 were evaluated. The groups' clinical characteristics did not differ, except for the relatively higher C-reactive protein (CRP) levels in the rhTM group (P = 0.0508). The survival rates of the rhTM and GM groups on days 7 and 30 were 92.3%, 69.2% and 80%, 70%, respectively, both group indicated similar mortality. However, on day 7, the platelet counts, SOFA scores, and CRP levels significantly improved in the rhTM group; the platelet counts and SOFA scores did not improve significantly in the GM group. The platelet counts of the rhTM group significantly improved compared to the GM group (P = 0.004). Recombinant human thrombomodulin might be more effective for sepsis-induced DIC than GM., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: The number of young surgeons in Japan has significantly decreased in recent years, which may lead to future problems in the medical field. Therefore, comprehensive training programs for young surgeons are needed., Design: Retrospective study, Setting: We developed a specific education program called the "Recruitment of Young Medical Apprentices" (RYOMA) project., Participants: We performed this project between January 2008 and August 2013 on fourth- to sixth-year medical students and internship doctors. The RYOMA project included step-by-step surgical education programs on open and scopic procedures as dry, wet, and animal laboratory training. Our goal was to increase the number of young and specialist surgeons., Results: Based on an interview questionnaire answered by 90 medical students, most young students were interested in surgical training and several chose to become surgeons in the future. The most positive opinions regarding the field of surgery were the impressive results achieved with surgery, whereas negative opinions included the difficulty of the surgical skill, physical concerns related to difficult work environments, and the severity of surgical procedures. The present program has begun to resolve negative opinions through adequate training or simulations. Of the 19 medical students and internship doctors who attended the RYOMA project in 2008, 17 trainees (90%) were satisfied with this special surgical program and 16 (88%) showed interest in becoming surgeons. The number of participants considering the field of surgery increased between 2008 and 2013. Of 23 participants, 19 (83%) had a positive opinion of the program after the training., Conclusions: Gaining experience in surgical training from an early stage in medical school and step-by-step authorized education by teaching staff are important for recruiting students and increasing the number of young surgeons., (Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Study Objective: To determine the perioperative frequency of deep vein thrombosis (DVT) after lower limb joint prosthesis surgery using Doppler ultrasonography (US)., Design: Prospective cohort study., Setting: Operating room and hospital ward., Patients: 144 consecutive ASA physical status 1 and 2 patients who underwent elective total hip arthroplasty (THA; n=64) or total knee arthroplasty (TKA; n= 80)., Interventions: Patients were allocated to two groups, those who developed DVT (DVT group) postoperatively and those who did not (no-DVT group). To examine the perioperative risk factors for DVT after THA or TKA, comparative analysis of the two groups was done., Measurements: Doppler US was performed on all patients from the bilateral femoral to lower limb to detect the existence of DVT postoperatively., Main Results: DVT was detected in 61 patients (42%), including three proximal DVT patients (2%). Preoperative elevated plasma D-dimer value [P = 0.0131, odds ratio (OR) 1.54, 95% CI 1.10-2.17] and history of hyperlipidemia (P = 0.0453, OR 6.92, 95% CI 1.04-46.00] were significant risk factors for the onset of DVT. A preoperative plasma D-dimer cutoff value as a diagnostic test was obtained as 0.85 μg/mL., Conclusions: A high preoperative plasma D-dimer value and/or history of hyperlipidemia were risk factors for DVT after THA or TKA., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Connective tissue diseases (CTD), such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD), develop pulmonary hypertension (PH). Generally all PH cases associated with any CTD are classified into the same PH group. However, histological examination shows both common and specific lesions for each disease. In patients with SLE, fibrosis is generally rare and mild. The findings of PH in SLE are similar to those in primary pulmonary hypertension. Many cases of SSc are accompanied by fibrosis. MCTD is rather close to SSc. Arterial and arteriolar lesions of MCTD are characterized by fibrous intimal thickening. In this review, we describe the pathological features of PH associated with each CTD.

Background: IL-13 is a major stimulator of inflammation and tissue remodeling at sites of Th2 inflammation, and common single-nucleotide polymorphisms in IL13 are associated with allergic phenotypes in several ethnically diverse populations. In particular, IL13Q110 is the non-conservative replacement of a positively charged arginine (R) with a neutral glutamine (Q) at position 110 of IL-13, and as we already know, individuals homozygous for glutamine (Q110/Q110) are strongly associated with asthma and IgE. IL13Q110 has been demonstrated to show that increased allergic inflammation depended on the enhanced IL-13-mediated Th2 effector function. Therefore, we investigated whether Q110/Q110 accelerated the decline in pulmonary function and development of airway remodeling of asthmatic patients in the general population., Methods: A total 336 asthmatic subjects living in Japan were recruited, genotyped, and had a pulmonary function test performed on them. To analyze airway inflammation and remodeling, bronchial lavage fluid (BLF) and endobronchial biopsy specimens were examined., Results: Forced expiratory volume in one second (FEV1), %predicted, forced expiratory volume/forced vital capacity ratio, and forced expiratory flow 25-75%, % predicted were significantly decreased in Q110/Q110 compared to R110/R110, and the decline in FEV1 was increased significantly in Q110/Q110 compared to R110/R110. The concentration of IL-13, IL-23, IL-11, GM-CSF, hyaluronic acid, and CCL8 in BLF were increased in Q110/Q110 compared to R110/R110 and the thickness of the subepithelial layer was thicker., Conclusions: Our study demonstrates that Q110/Q110 increases, at least in part, allergic inflammation and the propensity for airway remodeling, thus resulting in low lung function.

We describe a modification of Belghiti's liver hanging manoeuvre (LHM) using two small tubes placed in the cut planes, the first between the left lateral and medial sections, and the second along the right hepatic vein, to achieve complete anatomic central hepatectomy for a large tumour compressing surrounding vessels. Using this technique, a large central hepatocellular carcinoma compressing hilar vessels and the right hepatic vein was easily and safely resected in a 57-year-old man.

Aim: Cancer death in the early period after hepatectomy still occurs in patients with colorectal liver metastasis (CLM). We examined the relationship between clinicopathological parameters and survival periods in 130 CLM patients who underwent hepatectomy., Patients/methods: Patients were divided into four groups: Group 1 (5-year survivors without tumor relapse), Group 2 (survivors at 2-5 years), Group 3 (cancer death at 2-5 years), and Group 4 (cancer death within 2 years)., Results: A short surgical margin was frequent in Group 4 compared to Group 1 (31 vs. 78%, P<0.05). Primary node-positive status, absence of fibrous pseudo-capsular formation, higher Clinical Risk Score, and tumor recurrence within 12 months were frequent in Group 4 (P<0.05). Multivariate analysis revealed a short surgical margin (HR; 3.5) and early tumor relapse (HR; 5.9) as independently significant related parameters (P<0.05)., Conclusions: Sufficient surgical margins and careful follow-up for early tumor relapse may be important for improving postoperative outcomes for CLM patients.

Background: Histamine is known to have immunoregulatory roles in allergic reactions through histamine receptor 1 (H1R), H2R, H3R and H4R. However, its role in goblet cell hyperplasia in the airways of asthma patients is yet to be clarified., Objective: This study was designed to examine the role of histamine in goblet cell hyperplasia using histamine-deficient mice (Hdc-/- mice) with allergic airway inflammation., Methods: Wild-type and Hdc-/- C57BL/6 mice were sensitized with ovalbumin (OVA). After a 2-week exposure to OVA, goblet cell hyperplasia was evaluated. Cell differentials and cytokines in BALF were analyzed. The mRNA levels of MUC5AC and Gob-5 gene were determined quantitatively., Results: The number of eosinophils in BALF increased in both the sensitized wild-type mice and Hdc-/- mice with OVA inhalation. In addition, the numbers of alveolar macrophages and lymphocytes in BALF increased significantly in the sensitized Hdc-/- mice with OVA inhalation compared to the wild-type mice under the same conditions. The concentrations of Interleukin-4 (IL-4), IL-5, IL-13, Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and IL-2 in the BALF all increased significantly in both groups compared to those exposed to saline. In particular, the concentration of TNF-alpha in the Hdc-/- mice exposed to OVA was significantly higher than that in the wild-type mice under the same conditions. The mRNA levels of Gob-5 and MUC5AC, and the ratio of the goblet cells in the airway epithelium significantly increased in Hdc-/- mice exposed to OVA compared to wild-type mice., Conclusions: These results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.

Background/purpose: Large liver tumors often expand and severely compress intrahepatic vessels. In cases of the trisectionectomy for such tumors, however, it is difficult to adequately expose the transection planes. The liver hanging maneuver (LHM) is a useful technique for hemihepatectomy and an adequate transection plane might be also required in trisectionectomy., Methods: LHM procedure is basically followed by the Belghiti's method. A nasogastric tube was used for hanging. At the hepatic hilum, the tube was placed between the liver and Glisson's pedicle., Results: We report here the application of LHM for right and left trisectionectomy in patients with a large hepatoma in two cases. In case of a right trisectionectomy for a large tumor compressing the umbilical Glisson's pedicle, an adequate transection plane was obtained using the LHM because the resected and remnant livers rotated to the other side upon lifting the tube during transection. In case of a left trisectionectomy for a large hepatic tumor compressing the right hepatic vein, an adequate transection plane along the right hepatic vein was obtained using LHM as well., Conclusions: LHM is a useful surgical application for right and left trisectionectomy in patients with large liver tumors compressing the cut plane.

Basic polysaccharide strongly inhibited the hydrolysis of trioleoylglycerol (TO) emulsified with phosphatidylcholine and taurocholate by either pancreatic lipase or carboxylester lipase. DEAE-Sephadex dose-dependently inhibited the hydrolysis of TO by pancreatic lipase and carboxylester lipase; however, carboxymethyl-Sephadex and Sephadex G-50 did not inhibit the hydrolysis. Polydextrose (PD), a soluble polysaccharide, was a very weak inhibitor of pancreatic lipase. However, when a basic group, a DEAE group, was attached to PD, lipase inhibition by DEAE-PD was increased, and this was dependent on the substitution ratio of DEAE groups. The number of positive charges per PD molecule is important in lipase inhibition. Similar substitution effects were observed with other basic groups, such as piperidinoethyl and 3-triethylamino-2-hydroxypropyl. The natural basic polysaccharide, chitosan, also inhibited pancreatic lipase activity. Gel-filtration experiments suggested that DEAE-PD did not bind strongly to pancreatic lipase. The effect of DEAE-PD on TO hydrolysis by pancreatic lipase was studied using various emulsifiers: DEAE-PD (50 microg/ml) did not inhibit the hydrolysis of TO emulsified with arabic gum, phosphatidylserine, or phosphatidic acid. In vivo, oral administration of DEAE-PD to rats reduced the peak plasma triacylglycerol concentration and increased fecal lipid excretion. These results suggest that basic polysaccharide is able to suppress dietary fat absorption from the small intestine by inhibiting pancreatic lipase activity.

Background: Adiponectin is an adipose-derived hormone that plays a role in regulating metabolic processes such as fat partitioning and lipid and glucose metabolism. Quantification of adiponectin is useful for obtaining information on metabolic syndrome, but there is no rapid method to measure adiponectin for clinical use., Methods: We developed a rapid and sensitive latex particle-enhanced turbidimetric immunoassay (LTIA) using a latex bead-immobilized anti-adiponectin polyclonal antibody. The assay was performed on a Hitachi H7170 analyzer and evaluated for validity as a method to quantitate adiponectin, in parallel with the ELISA., Results: Dilution tests using LTIA showed linearity from 0.25 to 30 microg/ml. Within-run CV and total CV were obtained in the range of 0.8-1.9% and 1.1-2.0%, respectively. No interference was observed in the testing of specimens containing potentially interfering substances such as bilirubin, ditaurobilirubin, hemoglobin triglyceride, rheumatoid factor, type IV collagen, fibronectin, and complement factor (C1q). A strong correlation between LTIA and ELISA was confirmed (n=30, r=0.990, y=0.95x+0.39)., Conclusion: The LTIA assay is applicable to quantitating the serum concentration of adiponectin. This assay is more convenient and faster than ELISA and suitable for clinical routine analysis.

Matrix metalloproteinase-9 (MMP-9) is abundantly expressed in abdominal aortic aneurysms (AAAs), and it is considered to play a pivotal role in aneurysmal formation. Elevated circulating concentrations of MMP-9 have been reported in patients with AAA, but the influence of an operation on circulating MMP-9 is unclear. Therefore, to clarify the influence of an operation on circulating MMP-9 levels and to determine the role of MMP-9 in the progression of AAA, we measured serum MMP-9 levels in patients before and after AAA repair. Blood samples were obtained from 53 patients with AAA; 22 patients underwent AAA operations, including 17 patients with arterial occlusive disease (AOD), and nine normal control subjects. Serum MMP-9 levels were determined by an enzyme-linked immunosorbent assay. The serum MMP-9 concentration was significantly higher in AAA patients (622.0 +/- 400.2 ng/mL) than in either AOD patients (284.3 +/- 151.4 ng/mL) or healthy controls (280.8 +/- 165.5 ng/mL) (p < 0.001). The mean serum MMP-9 levels in patients undergoing surgery for AAA (268.1 +/- 215.9 ng/mL) was significantly lower than that in AAA patients (p < 0.01). Among the 10 patients whose sera were obtained preoperatively and postoperatively, the serum MMP-9 concentration fell significantly after the patients underwent the operation (p = 0.004). No significant difference was identified in serum MMP-9 concentrations among AOD patients, controls, and postoperative patients. These studies suggest that MMP-9 plays a pivotal role in aneurysm formation, and the circulating MMP-9 level is thus considered to reflect the biological behavior of the aneurysm.

Aims: The new Japanese staging system for hepatocellular carcinoma (HCC), the Japan integrated staging (JIS) score, accounts for both Child-Pugh classification and Japan tumour node metastasis (TNM) staging. However, in HCC patients who undergo hepatectomy, liver function is relatively good and a better prognostic classification of hepatic function is necessary., Methods: The present study was designed to analyse the modified JIS score using liver damage grade by the Liver Cancer Study Group of Japan instead of the Child-Pugh classification (using the category indocyanine green retention rate at 15 min [ICG(R15)] instead of encephalopathy), and to compare the Japan TNM stage in 101 patients who underwent resection of HCC., Results: The liver damage grade showed significantly better discrimination of disease-free and overall survival than did the Child-Pugh classification. The modified JIS score system showed significant differences of disease-free and overall survivals in each score and this system was superior for discriminating survivals compared with the TNM staging., Conclusions: The combined staging system of hepatic function, particularly ICG(R15), and tumour stage provides a better prediction of prognosis. The JIS score using the liver damage grade was a useful predictor of prognosis of HCC patients who underwent hepatic resection.

Aims: We aim to clarify the long-term outcomes after an additional radical operation following gasless video endoscopic transanal rectal tumour excision (gasless VTEM) of 'high-risk' T1 and T2 rectal cancer., Methods: Gasless VTEM involves modification of transanal endoscopic microsurgery (TEM) by incorporating a standard laparoscopic video camera without a CO(2) insufflation system. This study between 1993 and 2003 included six men and five women with a median age of 64 years (range, 36-79). Specimens resected by gasless VTEM revealed (1) high-risk T1 carcinomas with one of the following histological types: poorly differentiated, lymphovascular invasion, and massive invasion of the submucosa (submucosal invasion greater than 200-300 microm from the muscularis mucosa) and (2) T2 carcinomas., Results: Eight patients had a high-risk T1 carcinoma and three patients had a T2 carcinoma. In two patients with a high-risk T1 carcinoma, a residual tumour was found in the specimen resected by the additional radical surgery. At a median follow-up of 86.5 months (range, 63.2-110.5), none of the patients developed tumour recurrence. Although one patient died with cancer at another organ site (hilar cholangiocarcinoma of the liver) 87 months after the additional radical surgery, the other 10 patients are alive and disease free., Conclusions: This study revealed favorable long-term outcomes after additional radical surgery following gasless VTEM in patients with high-risk T1 and T2 carcinomas.

Aims: Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that undergoes increased expression in colorectal carcinomas, but its prognostic value is a topic of debate. The aim of this study is to clarify the prognostic value of PD-ECGF expression in colorectal carcinomas., Methods: PD-ECGF expression was measured by enzyme-linked immunosorbent assay in frozen materials from 134 colorectal cancer patients who had received curative resections. Patients were divided into high expression and low expression groups based upon selected cut-off value. Correlations among PD-ECGF expression, clinicopathologic features, and disease-free interval were studied by univariate and multivariate analysis. To evaluate the origin of PD-ECGF, serial sections of the 134 tumours were stained for PD-ECGF and CD68., Results: PD-ECGF expression in the normal mucosa was 34.4+/-15.5 (Units/mg protein) and the cut-off value was 65.4 (mean+2SD). There were no significant correlations between clinicopathological features and PD-ECGF expression. The disease-free interval for the high PD-ECGF expression group was significantly longer than that of the low expression group (P=0.05). A multivariate Cox's regression analysis revealed that high PD-ECGF expression is an independent factor for better outcome. In immunohistochemical study, almost all tumour cells were negative for PD-ECGF, but stromal macrophages were predominantly positive for PD-ECGF., Conclusions: The PD-ECGF expression originated from stromal macrophages was a predictor for favorable outcome after curative resections for colorectal cancer.

Aims: The new staging system proposed by the Cancer of the Liver Italian Program (CLIP) for hepatocellular carcinoma (HCC) accounts for both liver dysfunction and tumour characteristics. The present study was designed to analyze UICC TNM stage, CLIP and modified CLIP in 91 patients who underwent hepatic resection for HCC., Methods: In the modified CLIP, scoring of AFP was replaced by that of protein induced by vitamin K absence or antagonist II (PIVKA-II; predictive value, > or = 400 mAU/ml)., Results: After hepatic resection, 54 patients developed recurrent tumours. High PIVKA-II was a significant determinant of recurrence (p<0.05). However, a high score of the modified CLIP as well as those other staging systems did not correlate with tumour-recurrence rate. Univariate analysis showed that high TNM score, CLIP score and our modified CLIP score were significant predictors of poor prognosis. Multivariate Cox's analysis revealed that high PIVKA-II and high modified CLIP score were associated with higher risk for disease-free and overall survival as well as high TNM stage., Conclusions: Compared with the original CLIP, our modified CLIP was a better predictor of prognosis of HCC patients who underwent hepatic resection.

Aims: To clarify the prognostic value of preoperative serum levels of sialyl Tn antigen (STN) for survival of gastric cancer patients., Methods: Pre-operative serum levels of STN, sialyl Lewis(a)antigen (CA19-9) and carcinoembryonic antigen (CEA) were examined in 180 patients who underwent resection of gastric cancer. Patients were divided into high and low antigen groups on the basis of a selected diagnostic-based cut-off value. Correlation between high antigen serum levels, established clinicopathologic factors and prognosis was examined by univariate and multivariate analysis., Results: Twenty-eight patients (15.6%) were classified as high STN; 37 (20.6%) as high CA19-9; and 33 (18.3%) as high CEA. The survival time of the high STN, CA19-9 or CEA group was shorter than that of the respective low-antigen group (P<0.0001, P=0.0008 or P=0.0002, respectively). Patients with stage III/IV tumours with high STN had a shorter survival time that those with low STN (P=0.0004). Cox's regression with multiple covariates showed that high serum STN is an independent factor predicting a worse outcome in gastric cancer patients. Multiple logistic regression analysis revealed that high serum STN is an independent predictor for the development of liver metastasis., Conclusions: Pre-operative high serum levels of STN predict both liver metastasis and poor prognosis after resection for gastric cancer.

In this study, we examined the preoperative serum levels of sialyl Lewisa, sialyl LewisX, sialyl Tn, and carcinoembryonic antigen in 243 colorectal cancer patients in order to clarify the role of these antigens as prognostic factors after curative surgery. The patients were divided into two groups: low and high antigen groups (lower and higher than a selected diagnostic-based cut-off value). Patients with high serum levels of sialyl Lewisa and carcinoembryonic antigen had shorter disease-free intervals than those with low serum levels of the respective antigen, although sialyl Lewisx and sialyl Tn showed no significant differences. Multivariate analysis revealed that three independent prognostic variables, including depth of tumor invasion, lymph node metastasis, and serum sialyl Lewisa level, did prove to have value in predicting disease-free interval. In conclusion, among the four antigens examined in this study, the preoperative serum level of sialyl Lewisa is the only independent prognostic variable for recurrence after curative resection of colorectal cancer.

Hyaluronate plays a unique role in the cancer cell microenvironment. In particular, melanoma is the tumor type in which hyaluronate and hyaluronate recognition have been most closely linked to malignancy. In this study we show that a human melanoma cell line stably transfected with hyaluronate synthase cDNA displays enhanced motility. We used a fixed erythrocyte exclusion assay to isolate subsets of the WM793 human melanoma cell line that expressed either high or low amounts of hyaluronate. A cell line with a high level of hyaluronate on its surface (WM793H) displayed significantly higher cell motility on colloidal-gold-coated coverslips than did a line with a low level (WM793L). Next, in order to directly investigate the effects of hyaluronate on melanoma cell migration, we transfected cDNA encoding mouse hyaluronate synthase HAS1 or HAS2 into the re-cloned human melanoma cell line that produced a low amount of hyaluronate (WM793L) by the lipofection method. Several clonal transfectants differentially producing hyaluronate were obtained. There was a positive correlation between total hyaluronate synthesis and formation of the pericellular hyaluronate-rich matrix. We observed an increase in the migration ability of hyaluronate cDNA (HAS1 or HAS2)-transfected cells compared with control cells on glass plates covered with colloidal gold particles. A migration-inhibition assay with anti-CD44 monoclonal antibody showed blocking of the cell motility. It is speculated that the tumor cells might migrate through a hyaluronate-rich extracellular environment when they invade nearby host tissues and that hyaluronate production by the tumor cells could increase this migration. These results suggest that hyaluronate may play a role in the aggressiveness of human melanoma cells.

The cleavage signal transferred to the future cleavage cortex during anaphase has been proposed as "cleavage stimulus," but no signal has proved to induce cleavage furrows. The local Ca2+ transient along the cleavage furrow has been reported, but the Ca2+ source has remained unknown. To address these questions, we studied functions of Ca2+ stores in dividing newt eggs and found that microinjection of the Ca2+ store-enriched microsome fraction to the dividing newt egg induced a local extra-cleavage furrow at the injection site in 64-67% of the injected newt eggs while coinjection with inositol 1,4, 5-trisphosphate receptor (IP(3)R) antagonists heparin or anti-type 1-IP(3)R antibody clearly suppressed this induction (5 and 11% in induction rates, respectively). Injection of cerebellar microsomes from the type 1-IP(3)R-deficient mice induced extracleavage furrows albeit at a low rate (19%). Our observations strongly suggest that Ca2+ stores with IP(3)R induce and position a cleavage furrow via IP(3)-induced Ca2+ release (IICR) as Ca(2+)-releasing machinery and putative cleavage stimulus itself., (Copyright 1999 Academic Press.)

The expression of blood group antigens A, B, and H, as well as sialylated and nonsialylated forms of Lewis(a) and Lewis(x), was studied using immunohistochemical methods in normal and tumor tissues in the following cohort of patients: 51 patients with primary breast carcinoma, 13 with metastatic lymph node lesions, and 16 with benign tumors of the breast. As a control, normal tissue was obtained from a similar group of 22 patients with breast cancer. The noncancerous tissues expressed the same A/B/H antigens as the patients' red blood cells and also usually expressed Lewis-related antigens. Seventy-six percent of primary carcinomas failed to express the appropriate A/B/H antigens, and in one blood group A patient the tumor tissue expressed B antigen. In the metastatic lesions, Lewis(a)/sialyl Lewis(a) expression was reduced when compared with the primary tumors, but Lewis(x)/sialyl Lewis(x) antigens were still expressed. These results suggest a possible relationship between the metastatic behavior of the tumor and expression of the blood group antigens.

The superoxide-generating NADPH oxidase system in phagocytes consists of membrane-associated cytochrome b558 and three cytosolic components named p67-phox, p47-phox, and rac p21s. In a cell-free system consisting of membrane and cytosol, the oxidase can be activated with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and an unsaturated fatty acid such as arachidonic acid (AA). Incubation of cytosol and membrane with AA alone caused clear translocation of p47-phox and p67-phox to the membrane, but only slight translocation of rac p21s. GTP gamma S alone did not significantly induce the translocation of rac p21s. However, GTP gamma S in combination with AA markedly augmented rac p21s translocation to the membrane. The translocation of rac p21s is not induced by GDP or GDP beta S. These results indicate that the GTP-bound active form of rac p21s is the entity that is translocated to the membrane by the action of AA.