tbuckley/cabot-search huggingface dataset:
S131 Identifying Occupational Asthma Among a Cohort of Cleaners in the North East England
Authors: S Alfajjam, C Stenton, T Pless-mulloli, D Howel
Journal: Thorax (2012)

<h3>Introduction</h3> We have demonstrated a prevalence of asthma of 14% in a survey of 1400 UK hospital and university cleaners, and an estimated incidence of asthma of 3.3/1000 person-years. 26% of cleaners reported work-related symptoms. We have explored the possibility that these cleaners have occupational asthma using serial measurements peak expiratory flow (PEF) and airway responsiveness. <h3>Objectives</h3> To identify occupational asthma in a cohort of cleaners. <h3>Methods</h3> A respiratory symptom questionnaire was distributed among 1400 cleaners working in three local hospital trusts and two universities. Airway responsiveness (PD20) was measured in those with asthma symptoms using a methacholine challenge test. Those with measurable airway responsiveness (PD20 &lt;1600ug) were invited to undergo a repeat measurement away from work and to carry out serial PEF measurements that were analysed for a work-related effect using OASYS (Burge, Pantin et al. 1999). <h3>Results</h3> 557 (40%) returned the questionnaire and 167 reported respiratory symptoms. Of these, 56 (33.5%) attended for methacholine challenge testing. 26 (46%) had quantifiable results. 12 subjects underwent serial PD20 measurements at and away from work. Overall, there were no significant changes in airway responsiveness. Geometric mean PD20 at work was 193 ug and away from work was 254 ug (t=0.6; p=0.5). 5 cleaners showed a 3-fold or more increase in PD20 away from work raising the possibility of significant changes in those individuals. 10 subjects completed serial peak expiratory flow measurements. The mean OASYS score was 1.97. One subject had a score of &gt; 2.5 suggesting a work related effect. <h3>Conclusion</h3> Although the prevalence of asthma symptoms in our cohort is consistent with other epidemiological evidence showing a 1.5 to 2.0 fold risk of asthma, we found little evidence of occupational asthma using conventional clinical diagnostic tests in this group. The findings are consistent with the hypothesis that cleaners develop their asthma in an unusual way, possibly though a low dose irritant mechanism. Burge, P.S., C.F.A. Pantin, et al. (1999). “Development of an expert system for the interpretation of serial peak expiratory flow measurements in the diagnosis of occupational asthma.” Occupational and Environmental Medicine <b>56</b>(11): 758–764.
Abstract 571: PK and antitumor activity of DEBIO 0507, a new platinum derivative, in preclinical tumor models
Authors: Caroline Mignard, Virginie Bari, Francis Bichat, Lucienne Cicurel, Grégoire Vuagniaux, Maryse Barbier
Journal: Cancer Research (2010)

Abstract Background: Since the introduction of cisplatin, carboplatin and oxaliplatin, several new generations of platinum analogues have been developed as candidates for chemotherapy. DEBIO 0507/NC-4016 is a DACH-Platin Polymeric Micelle. The main objectives of this project were to assess pharmacokinetic (PK) profile of DEBIO 0507 and evaluate its efficacy in preclinical studies against a broad spectrum of experimental tumors including syngenic, xenogenic tumor models and a cisplatin-resistant cell line. Methods: PK and biodistribution studies were conducted in multiple matrices (blood, tumor, liver, spleen, kidneys and pancreas) collected in mice bearing C38 mouse colon carcinoma and treated with a single IV injection of DEBIO 0507 at 2 mg Pt/kg. Antitumor activity of DEBIO 0507 intravenously injected every 4, 7 or 14 days at different doses was investigated in C38 mouse colon carcinoma bearing C57BL/6 mice. Antitumor effect of DEBIO 0507 was also assessed in a panel of human tumor xenografted in nude mice, Calu-6 and A-549 human lung carcinoma, HT-29 human colon carcinoma, PC-3 human prostatic tumor, FaDu human pharynx carcinoma, NIH:OVCAR3 human ovarian tumor, BxPC-3 human pancreas tumor and HepG2 human hepatocarcinoma. Results: A concentration of 61 µg Pt/ml was detected in plasma from 5 minutes after injection and persisted during two hours. Platinum was very slowly cleared from plasma as it was still detected 14 days after injection (t1/2α : 40h). An accumulation was observed in tumor from 5 minutes to 8 days after injection and terminal elimination phase was very long since platinum was also detected 14 days after injection. The same PK and BD profiles were observed for other tissues. DEBIO 0507 was not active in the models of NIH: OVCAR3 human ovarian tumor, BxPC-3 human pancreas tumor and HepG2 human hepatocarcinoma. DEBIO 0507 exhibited a significant and dose-dependent antitumor activity against C38 mouse colon carcinoma when administered every 4, 7 or 14 days (optimal T/C of 0, 0 and 5%, respectively). We also demonstrated growth inhibitory effects of DEBIO 0507 in human PC-3 prostate, Calu-6 lung, FaDu head and neck and A-549 lung tumors xenografted in nude mice when injected with similar doses and schedules (optimal T/C of : 26, 29, 39 and 40%, for each model respectively). Conclusion: DEBIO 0507 displayed a marked antitumor activity against a large spectrum of tumor models associated with a long exposure of tumor to Pt. These preclinical results provide useful data to support the design of clinical trials for DEBIO 0507. DEBIO 0507/NC-4016 was produced by Nanocarrier Co.,Ltd. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 571.
Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis
Authors: Zhen Chen, Tsung-Ching Lai, Yi-Hua Jan, Feng-Mao Lin, Wei-Chi Wang, Han Xiao, Yun-Ting Wang, Wei Sun, Xiaopei Cui, Ying-Shiuan Li, Tzan Fang, Hongwei Zhao, Chellappan Padmanabhan, Ruobai Sun, Danny Ling Wang, Hailing Jin, Gar-Yang Chau, Hsien-Da Huang, Michael Hsiao, John Y-J. Shyy
Journal: Journal of Clinical Investigation (2013)

Despite a general repression of translation under hypoxia, cells selectively upregulate a set of hypoxia-inducible genes. Results from deep sequencing revealed that Let-7 and miR-103/107 are hypoxia-responsive microRNAs (HRMs) that are strongly induced in vascular endothelial cells. In silico bioinformatics and in vitro validation showed that these HRMs are induced by HIF1α and target argonaute 1 (AGO1), which anchors the microRNA-induced silencing complex (miRISC). HRM targeting of AGO1 resulted in the translational desuppression of VEGF mRNA. Inhibition of HRM or overexpression of AGO1 without the 3′ untranslated region decreased hypoxia-induced angiogenesis. Conversely, AGO1 knockdown increased angiogenesis under normoxia in vivo. In addition, data from tumor xenografts and human cancer specimens indicate that AGO1-mediated translational desuppression of VEGF may be associated with tumor angiogenesis and poor prognosis. These findings provide evidence for an angiogenic pathway involving HRMs that target AGO1 and suggest that this pathway may be a suitable target for anti- or proangiogenesis strategies.
S-Phase cells in diseased human liver determined by anin Vitro BrdU-anti-BrdU method
Authors: Akio Shimizu, Kazuo Tarao, Shouji Takemiya, Masaoki Harada, Tohru Inoue, Tetsuo Ono
Journal: Hepatology (1988)

Using a monoclonal antibody to bromodeoxyuridine, we studied the cell kinetics of human hepatocellular carcinoma, liver cirrhosis, chronic active hepatitis and alcoholic liver fibrosis. Specimens were taken either by biopsy or surgery and immediately incubated with 0.1% bromodeoxyuridine solution at 37°C for 45 min. After in vitro labeling, the bromodeoxyuridine taken up by the nuclei of S-phase cells was determined by the avidinbiotin-peroxidase complex method, using an anti-bromodeoxyuridine monoclonal antibody as the first antibody. The number of positive nuclei in 1,000 hepatic cells was counted, and the bromodeoxyuridine labeling index was expressed per thousand. The mean bromodeoxyuridine labeling index ± S.D. of the cancerous portion of hepatocellular carcinoma, the noncancerous portion of hepatocellular carcinoma, liver cirrhosis, chronic active hepatitis and alcoholic liver fibrosis were 64.1 ± 31.3, 33.6 ± 14.4, 23.2 ± 20.8, 9.1 ± 6.1 and 21.6 ± 13.0, respectively. The mean bromodeoxyuridine labeling index of the hepatocellular carcinoma cancerous portion was statistically higher than that of any other group. There was no statistical difference by the t test or the Wilcoxon test between the noncancerous portion of hepatocellular carcinoma and liver cirrhosis, and these two groups were proved interdependent by χ 2 test (Fisher’s exact test), whether they were subdivided by bromodeoxyuridine labeling index ±10 or not. Bromodeoxyuridine labeling index was not significantly correlated with the usual biochemical parameters such as serum AST, ALT, γ-GTP, alkaline phosphatase, lactate dehydrogenase, cholinesterase, albumin, and α-fetoprotein. These results suggest that the bromodeoxyuridine labeling index of biopsied or resected specimens could give valuable information on cell kinetics when analyzing liver diseases and could be especially useful in distinguishing hepatocarcinogenesis from hepatic cirrhosis.
Macroautophagy and chaperone-mediated autophagy are required for hepatocyte resistance to oxidant stress
Authors: Yongjun Wang, Rajat Singh, Youqing Xiang, Mark J. Czaja
Journal: Hepatology (2010)

The function of the lysosomal degradative pathway of autophagy in cellular injury is unclear, because findings in nonhepatic cells have implicated autophagy as both a mediator of cell death and as a survival response. Autophagic function is impaired in steatotic and aged hepatocytes, suggesting that in these settings hepatocellular injury may be altered by the decrease in autophagy. To delineate the specific function of autophagy in the hepatocyte injury response, the effects of menadione-induced oxidative stress were examined in the RALA255-10G rat hepatocyte line when macroautophagy was inhibited by a short hairpin RNA (shRNA)-mediated knockdown of the autophagy gene atg5. Loss of macroautophagy sensitized cells to apoptotic and necrotic death from normally nontoxic concentrations of menadione. Loss of macroautophagy led to overactivation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway that induced cell death. Death occurred from activation of the mitochondrial death pathway with cellular adenosine triphosphate (ATP) depletion, mitochondrial cytochrome c release, and caspase activation. Sensitization to death from menadione occurred despite up-regulation of other forms of autophagy in compensation for the loss of macroautophagy. Chaperone-mediated autophagy (CMA) also mediated resistance to menadione. CMA inhibition sensitized cells to death from menadione through a mechanism different from that of a loss of macroautophagy, because death occurred in the absence of JNK/c-Jun overactivation or ATP depletion. Hepatocyte resistance to injury from menadione-induced oxidative stress is mediated by distinct functions of both macroautophagy and CMA, indicating that impaired function of either form of autophagy may promote oxidant-induced liver injury.
Abstract P6-15-16: LIV-1 Antibody-Drug Conjugate: A Novel Therapeutic Agent for Breast Cancer
Authors: LM Smith, D Sussman, A Nesterova, L Westendorf, S Duniho, M Anderson, B Mbow, A Gregoire, J Hunter, N Whiting, CL Law, DR. Benjamin
Journal: Cancer Research (2010)

Abstract LIV-1, also known as SLC39A6 or ZIP6, is a member of the zinc transporter family and was first identified as an estrogen-inducible gene in breast cancer. LIV-1, as a downstream target of STAT3, promotes the epithelial to mesenchymal transition that is important in the malignant progression to metastasis. Consistent with its role in cancer, we determined by immunohistochemical (IHC) analysis that LIV-1 is expressed in 86% (n=22) of estrogen receptor-positive (ER+), hormone-treated tumors (both primary and metastatic sites), and in 65% (n=20) of ER-/PR-/Her2- (triple-negative) breast cancers. In healthy human tissues, LIV-1 expression is limited to hormonally-regulated organs (prostate, uterus, and breast). We generated an antibody-drug conjugate (ADC) consisting of a humanized anti-LIV-1 mAb conjugated to the antitubulin agent monomethyl auristatin E (MMAE), via a plasma stable, enzyme-cleavable linker (vc). The humanized LIV-1 mAb bound with high affinity to both human and cynomolgous LIV-1 (2-4 nM). In vitro, anti-LIV-1-vcMMAE showed specific cytotoxic activity against a MCF-7 cell line with an IC50= 78 ng/ml. In vivo studies also demonstrated antitumor activity of anti-LIV-1-vcMMAE in preclinical xenograft models, including MCF-7 breast cancer cell line, with significant delay of tumor growth compared to control groups. The broad expression of LIV-1 in both hormonally-treated and triple-negative tumors and the limited expression in vital organs make LIV-1 an excellent target for an ADC. These findings support the further development of anti-LIV-1-vcMMAE as a promising therapeutic agent for the treatment of ER+ and triple-negative breast cancers. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-15-16.
AN EFFECT OF ANTIGEN-ANTIBODY INTERACTION ON BLOOD COAGULATION
Authors: John Robbins, Chandler A. Stetson
Journal: The Journal of Experimental Medicine (1959)

Each of several antigen-antibody systems studied has been found to affect the coagulation mechanism in the rabbit, causing a marked shortening of the coagulation time in vitro of samples of whole blood maintained in siliconized glassware. Addition of specific antigen to the blood of actively immunized animals or addition of antigen-antibody mixtures to the blood of normal animals produced the effect. The coagulation time of plasma was not affected, indicating that the phenomenon may be mediated by an effect on platelets. This effect of antigen-antibody interaction may be involved in the production of tissue damage in vivo.
Apoptosis Protease Activator Protein-1 Expression Is Dispensable for Response of Human Melanoma Cells to Distinct Proapoptotic Agents
Authors: Marina Zanon, Adriano Piris, Ilaria Bersani, Claudia Vegetti, Alessandra Molla, Alessia Scarito, Andrea Anichini
Journal: Cancer Research (2004)

Abstract Loss of expression of the apoptosis protease activator protein-1 (APAF-1) in human melanoma is thought to promote resistance to programmed cell death by preventing caspase-9 activation. However, the role of the APAF-1–dependent pathway in apoptosis activated by cellular stress and/or DNA damage has been recently questioned. We investigated APAF-1 expression in a large panel of human melanomas and assessed cellular response to several proapoptotic agents in tumors expressing or lacking APAF-1 protein. In two melanomas with wild-type p53 but with differential expression of APAF-1, treatment with camptothecin, celecoxib, or an nitric oxide synthase inhibitor (1400W) significantly modulated expression of 36 of 96 genes in an apoptosis-specific cDNA macroarray, but APAF-1 mRNA levels were not induced (in APAF-1− cells) nor up-regulated (in APAF-1+ cells), a finding confirmed at the protein level. Treatment with cisplatin, camptothecin, etoposide, betulinic acid, celecoxib, 1400W, and staurosporine promoted enzymatic activity not only of caspases -2, -8, and -3 but also of caspase-9 in both APAF-1+ and APAF-1− tumor cells. Moreover, drug-induced caspase-9 enzymatic activity could be not only partially but significantly reduced by caspase-2, -3, and -8 –specific inhibitors in both APAF-1+ and APAF-1− tumor cells. In response to 1 to 100 μmol/L of cisplatin, camptothecin, or celecoxib, APAF-1+ melanomas (n = 12) did not show significantly increased levels of apoptosis compared with APAF-1− tumors (n = 7), with the exception of enhanced apoptosis in response to a very high dose (100 μmol/L) of etoposide. These results suggest that the response of human melanoma cells to different proapoptotic agents may be independent of their APAF-1 phenotype.
High-tone Deafness simulating Mental Defect
Authors: M. D. Sheridan
Journal: BMJ (1944)

disease allows of no more radical alternative the operative risk must be accepted, for success in obtaining a satisfactory collapse carries with it some prospect of improvement in the contralateral disease.The abandonment of the pneumothorax without thoracoscopy and the maintenance of an unsatisfactory collapse are both bad practice. Summary and ConclusionsThe state of 200 cases of unilateral internal pneumolysis 5 years after operation is reported.Of these cases 2 were lost sight of in this period. 133(66.5%) survived 5 years.71 (86.5%) of those cases in which a satisfactory collapse was obtained by operation survived 5 years, and 56 of these were well and working after 6 years: none of them had a satisfactory collapse before operation.A satisfactory collapse on one side seems to have greatly improved the prospect of survival in cases with bilateral cavitation.The. persistence of positive sputum 3 mnonths after division of adhesions indicates a poor prognosis.On the other hand a negative sputum improves the outlook in the " incomplete" and " ineffective" collapse groups.Tuberculous empyema, especially when secondary infection is present, is a serious complication, but it accounted for only 18% of the deaths in 5 years.If artificial pneumothorax is employed the aim should be to obtain the most complete collapse possible by the use of internal pneumolysis.
Journal Reading in an Undergraduate Curriculum
Authors: Arni Kristinsson
Journal: New England Journal of Medicine (1994)

To the Editor: Systematic journal reading is not generally a part of the medical school curriculum. Recognizing the importance of medical journals to the practice of modern medicine, we introduced journal reading as a formal part of the curriculum in students' final year in internal medicine at the University of Iceland. Each student received weekly copies of the Lancet and the New England Journal of Medicine, kindly donated by the journals' editors. The students were given anonymous questionnaires to fill out before, during, and after the course. Each week students selected one article from either journal, to be presented to . . .
Anatomically and Physiologically Based Reference Level for Measurement of Intracardiac Pressures
Authors: Michael Courtois, Peter G. Fattal, Sandor J. Kovács, Alan J. Tiefenbrunn, Philip A. Ludbrook
Journal: Circulation (1995)

Background Many reference levels have been proposed for the measurement of intracardiac pressures, but none have met with universal acceptance. In the first part of our study, we evaluated 10 cardiologists’ understanding of how hydrostatic pressure influences intracardiac pressures as measured with fluid-filled catheters. In the second part, we proposed and validated a new zero level (H): the uppermost blood level in the left ventricular (LV) chamber relative to the anterior chest wall for a patient in the supine position. A comparison was made of LV minimum diastolic pressure measured by reference to H versus measurements made with the zero level at midchest. Methods and Results Using two-dimensional echocardiography, we determined H in the LVs of seven normal patients (five male, two female; age, 49±9 years) undergoing routine cardiac catheterization. H was determined from a left parasternal short-axis view and calculated as the average distance between end diastole and end systole of the endocardium of the uppermost segment of the LV anterior wall below the fourth or fifth intercostal space of the left sternal border on the anterior surface of the chest wall, with the patient in the supine position. A micromanometer/fluid-filled lumen catheter was then positioned in the LV, and we compared the micromanometer LV minimum pressure (LVP min ) obtained when the reference fluid-filled transducer was aligned at midchest with the LVP min obtained when the reference fluid-filled transducer was aligned at H. LVP min referenced to a midchest fluid-filled external transducer was measured as 5.1±1.6 mm Hg (range, 2.4 to 7.2 mm Hg) versus −0.6±0.6 mm Hg (range, −1.6 to 0.4 mm Hg) when referenced to H ( P &lt;.001). A significant linear relation was found to exist between patient anterior-posterior chest diameter and the magnitude of hydrostatic pressure influences related to pressure referenced at midchest ( r =.88; P &lt;.01). Conclusions External fluid-filled transducers should be used with the goal of removing hydrostatic pressure and other influences so that the presence of subatmospheric pressure during diastole in any of the cardiac chambers is accurately measured. To achieve this goal, intracardiac pressure should be referenced to an external fluid-filled transducer aligned with the uppermost blood level in the chamber in which pressure is to be measured. The current practice of referencing the zero level of LV diastolic pressure to an external fluid-filled transducer positioned at the midchest level results in systematic overestimation due to hydrostatic effects and produces physiologically significant error in the measurement of diastolic intracardiac pressure.
Burn Wound Closure With Cultured Autologous Keratinocytes and Fibroblasts Attached to a Collagen-Glycosaminoglycan Substrate
Authors: John F. Hansbrough
Journal: JAMA (1989)

Improved survival of patients with extensive burn injuries requires the development of better techniques for timely and permanent closure of the full-thickness wound. We developed procedures for establishing confluent, stratified layers of cultured, autologous keratinocytes on the surface of a modified collagen-glycosaminoglycan membrane that contains autologous fibroblasts. We transferred the composite grafts onto limited areas of excised full-thickness burn wounds of four patients with extensive burn injuries. Our results indicate that this composite graft material has acceptable "take," with formation of a basement membrane within 9 days of graft placement. Use of this technique for major wound coverage may offer a significant advance in the care of extensively burned patients and also may be useful for providing skin for reconstructive surgery.
Gene expression profiles of the collecting duct in the mouse renal inner medulla
Authors: Masaru Takenaka, Enyu Imai, Yasuyuki Nagasawa, Yasuko Matsuoka, Toshiki Moriyama, Tetsuya Kaneko, Masatsugu Hori, Shoko Kawamoto, Kousaku Okubo
Journal: Kidney International (2000)