tbuckley/cabot-search huggingface dataset:
Depletion of Protease‐Activated Receptor 2 but Not Protease‐Activated Receptor 1 May Confer Protection Against Osteoarthritis in Mice Through Extracartilaginous Mechanisms
Authors: Miriam T. Jackson, Babak Moradi, Sanaa Zaki, Margaret M. Smith, Sharon McCracken, Susan M. Smith, Christopher J. Jackson, Christopher B. Little
Journal: Arthritis & Rheumatology (2014)

Objective To explore the involvement of protease‐activated receptor 1 (PAR‐1) and PAR‐2 in the pathologic processes of osteoarthritis (OA) and to identify the cells/tissues primarily affected by ablation of PAR‐1 or PAR‐2 in mice. Methods OA was induced in the joints of wild‐type (WT), PAR‐1 +/+ , PAR‐1 −/− , and PAR‐2 −/− mice by destabilization of the medial meniscus (DMM), and scores of histologic features (cartilage aggrecan loss and erosion, subchondral bone sclerosis, osteophytes, and synovitis) were compared at 1, 4, and 8 weeks post‐DMM. The effects of PAR ablation on cartilage degradation and chondrocyte metalloproteinase expression/activity were studied in cultures of mouse femoral head tissue with or without interleukin‐1α (IL‐1α). At 1 week post‐DMM, synovial expression of cytokines and metalloproteinase genes was measured by reverse transcription–polymerase chain reaction, and populations of inflammatory cells were quantified by flow cytometry. Results Deletion of PAR‐2, but not that of PAR‐1, in mice significantly delayed the progression of cartilage damage and inhibited subchondral bone sclerosis following DMM. There was no inhibitory effect of PAR‐1 or PAR‐2 ablation on IL‐1α–induced cartilage degradation or chondrocyte metalloproteinase expression/activation. A low but significant level of synovitis persisted in mice subjected to DMM compared to that in control mice subjected to sham surgery, but no differences between the genotypes were seen 4 or 8 weeks post‐DMM. One week after DMM, increased synovial expression of proinflammatory cytokines and metalloproteinase genes, along with increased levels of CD4+ T cells, inflammatory monocytes, and activated macrophages, were seen in all genotypes. However, there was a significant reduction in the percentage of activated macrophages in PAR‐2 −/− mice compared to PAR‐1 −/− and WT mice. Conclusion Deletion of PAR‐2, but not that of PAR‐1, results in a significant decrease in DMM‐induced cartilage damage. The chondroprotection in PAR‐2 −/− mice appears to occur indirectly through modulation of extracartilaginous events such as subchondral bone remodeling and synovial macrophage activation, rather than through alteration of chondrocyte catabolic responses.
METASTASIS OF HETEROLOGOUSLY TRANSPLANTED TUMORS.
Authors: Harry S. N. Greene, Elizabeth K. Harvey
Journal: Cancer Research (1964)

The present investigation was undertaken in an attempt to determine the factors concerned in the failure of heterologously transplanted tumors to metastasize. Fragments of organs from hamsters bearing brain growths of the Brown-Pearce and V2 rabbit tumors were transplanted to the brains of normal hamsters and to the eyes of rabbits. The occurrence of tumor growth in the organ transplants demonstrated that both of the tumors were capable of vascular invasion and blood passage in the alien host.
Maximum-tolerated dose defined for single-agent gemcitabine: a phase I dose-escalation study in chemotherapy-naive patients with advanced non-small-cell lung cancer.
Authors: F V Fossella, S M Lippman, D M Shin, P Tarassoff, M Calayag-Jung, R Perez-Soler, J S Lee, W K Murphy, B Glisson, E Rivera, W K Hong
Journal: Journal of Clinical Oncology (1997)

PURPOSE We conducted a phase I trial of the novel nucleoside analog, gemcitabine, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose and efficacy in this population. PATIENT AND METHODS Eligibility requirements included stage III or IV NSCLC, performance status &lt; or = 1, and no prior chemotherapy. Gemcitabine was administered as a 30-minute intravenous infusion weekly for 3 weeks every 4 weeks. We enrolled patients at doses that ranged from 1,000 to 2,800 mg/m2/wk (three patients per cohort). Responses were assessed after every two courses (8 weeks). RESULTS We treated 33 chemotherapy-naive patients with stage III (n = 5) or IV (n = 28) NSCLC. Most had performance status 1, and 67% had adenocarcinoma. Eight of 32 assessable patients (25%) achieved a partial response. The projected median survival duration (all patients) is 49 weeks. The maximum-tolerated dose was 2,200 mg/m2/wk for 3 weeks every 4 weeks; dose-limiting toxicity was myelosuppression and reversible transaminase elevation. Other side effects were consistently mild. The maximum dose-intensity achieved with the first two cycles was 2,362 mg/m2/wk for 3 weeks every 4 weeks, which is a feasible phase II starting dose. CONCLUSION This study estimates a phase II starting dose of gemcitabine in chemotherapy-naive patients to be 2,400 mg/m2/wk for 3 consecutive weeks every 4 weeks; this is much higher than that previously reported in heavily pretreated patients. Twenty-five percent of patients with advanced NSCLC achieved a partial response to gemcitabine. This significant activity in conjunction with a very favorable toxicity profile supports the further evaluation of gemcitabine in combination with other active agents.
Effect of strenuous exercise on serum lithium level in man
Authors: J W Jefferson, J H Greist, P J Clagnaz, R R Eischens, W C Marten, M A Evenson
Journal: American Journal of Psychiatry (1982)

The authors examined the effect of strenuous exercise on the serum lithium levels of four healthy, conditioned athletes who were stabilized on lithium carbonate for 7 days and who ran a 20-km race under hot, humid conditions. The subjects became substantially dehydrated during the race, and their serum lithium levels decreased, suggesting that sweat lithium loss may be substantial. (The sweat-to-serum ratio for lithium exceeded that for sodium by a factor of 4.) The authors conclude that contrary to widely held belief, heavy sweating may not increase the risk of lithium intoxication.
Abstract 1229: Molecular Mechanisms of Angiotensin II-Mediated Mitochondrial Dysfunction: Linking Mitochondrial Oxidative Damage and Vascular Endothelial Dysfunction
Authors: Abdulrahman Doughan, David Harrison, Sergey Dikalov
Journal: Circulation (2007)

Mitochondrial (mito) dysfunction is a prominent feature of most cardiovascular diseases including hypertension, diabetes, and heart failure. Angiotensin II (Ang II) is an important stimulus for atherogenesis and hypertension; however, its effects on mito function remain unknown. We hypothesized that Ang II may induce mito oxidative damage that in turn may decrease endothelial nitric oxide (NO • ) and promote vascular oxidative stress. Mitochondria isolated from control and Ang II (200 nM, 4 hours) treated bovine aortic endothelial cells II were investigated. Electron Spin Resonance was used to study the effect of Ang II on mito ROS production, mito respiration, glutathione content and endothelial NO • . Mitochondrial membrane potential was examined using fluorescence microscopy. Endothelial O 2− • formation was quantified using an HPLC-based dihydroethidium assay. Mitochondrial H 2 O 2 and endothelial O 2− • production increased significantly after treatment of endothelial cells with Ang II. This increase was blocked by preincubation of intact cells with apocynin (NADPH oxidase inhibitor), uric acid (scavenger of peroxynitrite), chelerythrine (PKC inhibitor), N (G)-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor), 5-hydroxydecanoate (5-HD, mitochondrial ATP-sensitive potassium channels inhibitor) or glibenclamide. Depletion of p22phox subunit of NADPH oxidase with siRNA led to significant (P&lt;0.001) reduction in Ang II-mediated mito ROS production. Angiotensin II decreased mito glutathione content, and mito respiratory control ratio. These responses were attenuated by apocynin, 5-HD and glibenclamide. In addition, 5-HD prevented the Ang II-induced decrease in endothelial NO • (73% in Ang II-treated cells and 94% in Ang II plus 5-HD vs. 100% in control; P &lt; 0.05) and mito membrane potential. These events were not associated with activation of caspase-3. Angiotensin II induces mito dysfunction via a pathway that depends on PKC, the NADPH oxidase and formation of peroxynitrite. Furthermore, mito dysfunction in response to Ang II modulates endothelial NO • and O 2− • generation, which may in turn have ramifications for the development of endothelial dysfunction.
CD34+CD33- cells influence days to engraftment and transfusion requirements in autologous blood stem-cell recipients.
Authors: A L Pecora, R A Preti, G W Gleim, A Jennis, K Zahos, S Cantwell, L Doria, R Isaacs, A P Gillio, M A Michelis, J A Brochstein
Journal: Journal of Clinical Oncology (1998)

To evaluate the reliability of CD34/CD33 subset enumeration as a predictor of hematopoietic repopulating potential in autologous blood stem-cell transplantation and to determine which patient and treatment-related factors affect the timing, quantity, and type of blood stem cells mobilized.We analyzed blood stem-cell collections from 410 consecutive cancer patients who received mobilization therapy and evaluated factors, including CD34+ subset quantities, that might influence engraftment kinetics and transfusion requirements in autologous blood stem-cell recipients.The majority of patients (97%) mobilized CD34+33- cells, which were usually collected in the greatest quantity on the first day of apheresis. Patients who received only growth factor mobilized the highest percentage of CD34+33- cells. Extensive prior chemotherapy limited the collection of CD34+33- cells. In addition to patient diagnosis (P < .006) and total CD34+ cell dose (P = .0001), CD34+33- cell dose (P < .005) and percentage of CD34+33- cells (P < .005) were identified as independent factors significantly predictive of engraftment kinetics. CD34+33- cell dose (R2 < or = .177; P < .0001) was a strong and the only significant predictor of RBC and platelet transfusion requirements. Furthermore, independent of the total CD34+ cell dose, as the CD34+33- cell dose increased, days to neutrophil recovery, days to platelet recovery, and transfusion requirements decreased.These findings show that CD34+33- cells are readily collected in most cancer patients and significantly influence engraftment kinetics and transfusion requirements in autologous blood stem-cell recipients. CD34+33- cell quantity of the blood stem-cell graft appears to be a more reliable predictor of hematopoietic recovery rates than total CD34+ cell quantity in this setting.
Prognostic factors for patients with invasive ductal carcinoma of the breast who received neoadjuvant chemotherapy
Authors: N. Tamura, N. Tamura
Journal: Journal of Clinical Oncology (2009)

e11617 Background: Neoadjuvant chemotherapy (NAC) for patients with invasive ductal carcinoma (IDC) of the breast is performed as a standard therapy in many hospitals for improving outcomes of IDC patients. The purpose of this study is to identify important prognostic clinicopathological factors for 115 IDC patients who operated in our hospital (1997 to 2002) followed by NAC. Methods: The multivariate analyses with an assessment of pathological effect of NAC, grading system for lymph vessel tumor emboli (LVTE), and histological factors of tumors in lymph nodes in addition to well-known prognostic clinicopathological factors were performed in IDC patients with nodal metastasis and in those of pTNM stage III as well as IDC patients as a whole. Results: Multivariate analyses demonstrated that grading system for LVTE was a significant prognostic factor for IDC patients in the both group. Severe tumor stroma in nodal metastatic tumors significantly increased the HRs of tumor recurrence of IDC patients in the both group. Number of mitotic figures in nodal metastatic tumors significantly increased the HRs of tumor death in IDC patients with nodal metastasis. Tumor necrosis in primary-invasive-tumors was a significant factor for tumor recurrence of patients in the both. Conclusions: The study clearly demonstrated that grading system for LVTE, and characteristics of nodal metastatic tumors as well as the presence of tumor necrosis in primary-invasive tumors are very important prognostic factors for IDC patients who received NAC. Since we already reported a prognostic significance of the factors in IDC patients who did not receive NAC in previous studies, we concluded that the factors are also very important for IDC patients who received NAC to accurately assess their outcome. No significant financial relationships to disclose.
Abstract LB-129: Identifying tumor subpopulations and the functional consequences of intratumor heterogeneity using single-cell profiling of breast cancer patient-derived xenografts
Authors: Paul Savage, Sadiq M. Saleh, Ernesto Iacucci, Timothe Revil, Yu-Chang Wang, Nicholas Bertos, Anie Monast, Hong Zhao, Margarita Souleimanova, Keith Szulwach, Chandana Batchu, Atilla Omeroglu, Morag Park, Ioannis Ragoussis
Journal: Cancer Research (2015)

Abstract Human breast tumors have been shown to exhibit extensive inter- and intra-tumor heterogeneity. While recent advances in genomic technologies have allowed us to deconvolute this heterogeneity, few studies have addressed the functional consequences of diversity within tumor populations. Here, we identified an index case for which we have derived a patient-derived xenograft (PDX) as a renewable tissue source to identify subpopulations and perform functional assays. On pathology, the tumor was an invasive ductal carcinoma which was hormone receptor-negative, HER2-positive (IHC 2+, FISH average HER2/CEP17 2.4), though the FISH signal was noted to be heterogeneous. On gene expression profiling of bulk samples, the primary tumor and PDX were classified as basal-like. We performed single cell RNA and exome sequencing of the PDX to identify population structure. Using a single sample predictor of breast cancer subtype, we have identified single basal-like, HER2-enriched and normal-like cells co-existing within the PDX tumor. Genes differentially expressed between these subpopulations are involved in proliferation and differentiation. Functional studies distinguishing these subpopulations are ongoing. Microfluidic whole genome amplification followed by whole exome capture of 81 single cells showed high and homogeneous target enrichment with &amp;gt;75% of reads mapping uniquely on target. Variant calling using GATK and Samtools revealed founder mutations in key genes as BRCA1 and TP53, as well as subclonal mutations that are being investigated further. Loss of heterozygocity was observed in 16 TCGA cancer driver genes and novel mutations in 7 cancer driver genes. These findings may be important in understanding the functional consequences of intra-tumor heterogeneity with respect to clinically important phenotypes such as invasion, metastasis and drug-resistance. Citation Format: Paul Savage, Sadiq M. Saleh, Ernesto Iacucci, Timothe Revil, Yu-Chang Wang, Nicholas Bertos, Anie Monast, Hong Zhao, Margarita Souleimanova, Keith Szulwach, Chandana Batchu, Atilla Omeroglu, Morag Park, Ioannis Ragoussis. Identifying tumor subpopulations and the functional consequences of intratumor heterogeneity using single-cell profiling of breast cancer patient-derived xenografts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-129. doi:10.1158/1538-7445.AM2015-LB-129
Influence of patient activation and health literacy on quality of life among patients with COPD
Authors: David Coultas, Bradford Jackson, Karan Singh, Sejong Bae
Journal: European Respiratory Journal (2012)

Background: While many factors contribute to the health status of patients with COPD little attention has been given to the influence of patient activation (PA) and health literacy (HL).  Objectives: The purpose of this analysis was to examine the influence of PA and HL on quality of life (QOL) among a sample of patients with COPD.  Methods: This was a cross-sectional analysis of baseline data from patients with COPD eligible for pulmonary rehabilitation enrolled in a self-management clinical trial. PA was measured using two questions: confidence on when to seek medical care (ACT1) and frequency of taking a list of medications to doctor visits (ACT2). HL was measured using three questions: confidence in filling out forms, frequency of help needed to read hospital materials, or problems learning about medical condition. QOL was measured using generic (SF-12) and disease-specific (Chronic Respiratory Questionnaire [CRQ]) instruments.  Results: Of 218 patients the majority reported being confident/very confident when to seek medical care (ACT1=79.8%) and taking a list of medicines (ACT2=63.8%). The association between levels of PA and QOL was examined separately using linear regression: ACT1 was directly and significantly associated with CRQ, and SF-12 physical and mental composite scores. In contrast ACT2 was only significantly, but inversely associated with CRQ. There was no association between levels of HL and any measures of QOL.  Conclusion: These results suggest that a component of patient activation (ACT1) is associated with improved QOL and may offer a specific target for intervention to enhance activation and outcomes.  Funding: National Institutes of Health-NHLBI R18 HL092955.
Doctors take to Twitter to refute Hunt’s claim that NHS has weekday working culture
Authors: Gareth Iacobucci
Journal: BMJ (2015)

Hundreds of doctors have taken to social media to directly challenge the health secretary for England’s claim that hospitals “do not have a proper seven day service,” causing thousands of unnecessary deaths in the NHS.

In a mocking riposte to Jeremy Hunt, hundreds of medical professionals posted pictures of themselves at work on the weekend of 17-19 July on …
Index of myocardial injury CIIS and mortality of patients with chronic obstructive pulmonary disease
Authors: Nina Karoli, Andrey Rebrov
Journal: European Respiratory Journal (2011)

Aim of the study was to assess informative power of the Cardiac Infarction Injury Score (CIIS) in patients with chronic obstructive pulmonary disease (COPD) to determine the role of CIIS in prognosis of death of patients with COPD.  We examined 124 patients with COPD (mean age 54,93±0,63 yrs) and followed 76 of them for 4 years. During follow up 16 patients (21.1%) died. COPD was diagnosed according GOLD criteria.The Cardiac Infarction Injury Score (CIIS) is an electrocardiographic classification system that was developed as a diagnostic tool to assess the extent of cardiac injury in myocardial infarction.  12.1% patients had CIIS>20 compared of only 5.6% patients whom had a recognised history of MI. In patients with COPD III-IV stage CIIS > 20 was detected 1.8 times more often than in patients with COPD I-II stage. Difference in CIIS between survivors and those who died was significant (p  Unrecognised MI is common in patients with COPD. We demonstrated that CIIS can be used for stratification of risk of death in patients with COPD. CIIS above 20 is defined as prognostically unfavorable factor or as risk factor of death in patients with COPD while CIIS
Endoscopic management of coloanal anastomotic disruption: a pilot case
Authors: Darren Chan, Surendra Mantoo
Journal: Endoscopy (2015)

A 65-year-old man with stage IIB moderately differentiated rectal adenocarcinoma, 6 cm from the anal verge on digital rectal examination, underwent ultra-low anterior resection with coloanal anastomosis and defunctioning loop ileostomy. The anastomosis was 4 cm from the anal verge.
Respiratory effects of tear gas inhalation
Authors: Eda Uslu, Gulcihan Ozkan, Cagla Uyanusta Kucuk, Hilal Onaran, Cagla Pinar Tastan Uzunmehmetoglu, Aslihan Ilgaz, Gamze Ayar, Makbule Ozlem Akbay, Hikmet Firat, Tansu Ulukavak Ciftci, Serdar Akpinar, Bulent Ciftci, Selma Firat Guven, Selen Bilekli, Arif Muezzinoglu, Fatih Torlak, Peri Arbak, Elif Dagli
Journal: European Respiratory Journal (2014)

On limited data on healthy volunteers and experimental animals, tear gas is accepted as a safe crowd control agent. There is not adequate information about the respiratory effects of recurrent tear gas inhalation.  The aim of this study is to investigate the frequency and duration of acute respiratory symptoms developed after the use of crowd control gases on public.  A face-to-face questionnaire survey was carried out among individuals who had involuntarily inhaled tear gas during public protests in June 2013 in Turkey.  Of those 546 people who participated in the survey 86 had been exposed to tear gas in Ankara and 460 in Istanbul. The average age was 31.2 years, 48% female, 52% male, 52% university graduates, 21%university students, 62% smokers. 40% was exposed to tear gas outdoors in close proximity, 24% were exposed indoors. 70% reported to have respiratory difficulty, 80% cough, 45% sputum production, 43% chest pain, 3% hemoptysis. The symptoms of nasal discharge were reported in 72% and eye redness in 81%, skin irritation in 44%. The median duration of symptoms were for respiratory difficulty 2 days, cough 15 days, sputum 14 days, hemoptysis 14 days, chest pain 15 days, nasal discharge 13 days, eye redness 14 days, skin irritation 15 days.  Tear gas was found to cause severe acute upper and lower airway symptoms in the study group with a high smoking rate. Contrast to the previous knowledge about the safety and short-time effects of crowd control agents, the symptoms were reported to last up to 2 weeks. Recurrent, indoor and short distance exposure in real life may have significant impact on respiratory system especially among smokers. The use of tear gas on humans should not be allowed unless safety can be proven by further studies.
Faecal Urobilinogen Levels and pH of Stools in Population Groups with Different Incidence of Cancer of the Colon, and Their Possible Role in its Aetiology
Authors: S L Malhotra
Journal: Journal of the Royal Society of Medicine (1982)

Mean faecal urobilinogen levels and the pH of stools were both found to be higher in subjects from a population group at high risk of developing cancer of the colon than in subjects matched for age, sex and socioeconomic status from a low-risk population group. An alkaline reaction of the colon contents seems to have a tumorigenic effect by a direct action on the mucus of the mucous cells. An acidic reaction, on the other hand, appears to be protective. These differences are dependent on the patterns of diet and manner of eating. Proper mastication of food, roughage, cellulose and vegetable fibre, and short-chain fatty acids of milk and fermented milk products in the diet appear to be protective.