tbuckley/cabot-search huggingface dataset:
Do field walking tests produce similar cardiopulmonary demands as an incremental treadmill test in obesity
Authors: Rachael Evans, Thomas Dolmage, Priscila Robles, Roger Goldstein, Dina Brooks
Journal: European Respiratory Journal (2012)

Cardio-respiratory fitness assessed by peak oxygen uptake (VO2pk) is an independent predictor of mortality in obesity. We investigated whether VO2pk measured during corridor walking tests was similar to that measured by an incremental treadmill (ITM) test in obesity.

Methods 

Individuals with a BMI >30 were recruited from a sleep clinic. All patients had treated Obstructive Sleep Apnea. Patients with chronic lung or heart disease were excluded. Participants completed an ITM test; the gold standard to determine VO2pk, two six-minute walk tests (6MWT) and two incremental shuttle walk tests (ISWT) on three separate days in a randomised order. Expired gas analysis was performed during all tests. The difference between the peak parameters for the two corridor tests compared to the ITM was assessed by Dunnett test.

Results 

16 patients completed the study: 8 male, mean [SD] age 58 [12] y, BMI 36.1 [7.6] kg/m2. The results of the second walking test were used. Table 1 shows the peak parameters for the three tests.

View this table:

Table 1





The limits of agreement for VO2 pk between the ISWT and the ITM was 730 ml/min.

Conclusion. 

In obesity, the ISWT VO2 pk more closely reflects ITM VO2pk than the 6MWT VO2pk, but is not predictive in an individual.
Abstract 394: TET1, which act as an tumor suppressor gene, is suppressed by DNA hypermethylation in gastric cancer
Authors: Jong-Lyul Park, Oh-Hyung Kwon, Kyu Sang Song, Seon-Young Kim, Yong Sung Kim
Journal: Cancer Research (2014)

Abstract 5-hydromethylcytosine (5hmC) is a hydroxmethylated form of DNA cytosine catalyzed by TET proteins. Recently, it was reported that aberrant regulation of 5hmC is associated with many cancers such as breast cancer, glioma, leukemia and melanoma. In this study, we examined the status of 5hmC and the role of TET1, which converts 5mC to 5hmC, in gastric cancer. Dot blot and ELISA assay results revealed global loss of 5hmC level in gastric cancer, and that decreased TET1 expression was associated with decreased 5hmC levels. Importantly, in gastric cancer patients, TET1-low group had advanced metastasis and poor survival compared with TET1-high group. To understand the mechanisms of TET1 suppression in gastric cancer, we performed pyrosequencing in 80 paired normal and tumors samples from gastric cancer patients, and found that the promoter region of TET1 was hypermethylated in tumors than adjacent normal tissues. Treating AGS cells with 5-Aza-2′deoxycytidine (Aza-dC) restored the expression of TET1. Transient transfection of in vitro transcribed TET1 mRNA into AGS cells significantly reduced the growth of AGS cells. In summary, our results showed that DNA methylation is responsible for the suppression of TET1 which has a tumor suppressor role in gastric cancer Citation Format: Jong-Lyul Park, Oh-Hyung Kwon, Kyu Sang Song, Seon-Young Kim, Yong Sung Kim. TET1, which act as an tumor suppressor gene, is suppressed by DNA hypermethylation in gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 394. doi:10.1158/1538-7445.AM2014-394
Extracts from responses
Authors: John M Reay
Journal: BMJ (2008)

The instruction to prescribe antibiotics for all patients with acute otitis media in the 10-minute consultation contradicts guidance published elsewhere, which indicates that antibiotics should not be prescribed in most cases.1 2 Educating patients, in particular parents of small children, that all earache does not need to be seen by a GP or out of hours doctor has workload implications.
Mechanisms of toxicity induced by nitric oxide in human lymphoblastoid cells expressing wild-type and null p53
Authors: Chun-Qi Li, Laura J. Trudel, Gerald N. Wogan
Journal: Cancer Research (2004)

767  Nitric Oxide (NO) induces cell death and mutagenesis in many in vitro and in vivo experimental models. Biochemical mechanisms through which NO induces cytotoxicity and genotoxicity are unclear. In this study, human lymphoblastoid TK6 cells harboring wild-type p53 and isogenic p53 null NH32 cells were exposed for 1.5 to 16 hours to NO, delivered into the culture medium by diffusion through permeable tubing, at a steady state concentration of 0.6 μM, similar to levels estimated to occur in vivo in inflamed tissues. Thresholds for NO-induced cell death were shown to be 150 μM min in TK6 cells and 300 μM min in NH32 cells. In further experiments, three NO doses for each cell type, namely, 50% of threshold (sublethal), threshold, and 2X threshold (toxic) were used to investigate mechanisms of cell death. In TK6 cells, threshold (150 μM min) or higher (300 μM min), but not sublethal (50 μM min) doses, induced extensive DNA double-strand breaks. In contrast, no DNA double-strand breaks were detected in NH32 cells, even after treatment with a toxic dose (600 μM min). Threshold and toxic doses of NO induced mutagenesis of the TK1 gene in NH32 cells, whereas only the toxic dose was effective in TK6 cells. Increases in TK1 mutant fraction in NH32 cells were substantially greater than in TK6 cells. Mitochondrial membrane potential loss and apoptosis were lower in NH32 cells than in TK6 cells. NO treatment caused depletion of cellular glutathione (GSH) in both cell lines in a dose- and time-dependent manner. In both cell lines, sublethal doses caused GSH depletion but no loss in viability. By comparison, treatment of TK6 cells with 125 μM BSO (L-buthionine SR-sulfoximine) also caused virtually complete GSH depletion, but no cell death up to 48 hours after treatment. Intracellular GSH level partially recovered during 24 to 48 hours following depletion. Prior GSH depletion by BSO did not increase sensitivity to NO-induced cell killing. Toxic NO doses caused reduced Cu/Zn-superoxide dismutase (SOD1) protein expression, measured by Western blot, in TK6 cells, but increased expression in NH32 cells. Under the same conditions, levels of catalase protein were upregulated only in TK6 cells, and GSH peroxidase levels were unchanged in both cell types. Survival signaling proteins NF-κB p50 and p65, and Akt were suppressed only in TK6 cells. Taken together, these data indicate that mechanisms of toxicity induced by NO in cells expressing wild-type p53 differ from those in isogenic p53 null cells, and that p53 modulates cell death through regulation of oxidative stress and survival signaling proteins. SOD1 and catalase, but not GSH peroxidase, may be p53 target proteins that play important roles in NO-induced stress responses. Although NO effectively induces GSH depletion, this alteration does not appear to be a critical initiating factor for cell death in these human lymphoblastoid cell lines.
Abstract 632: Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing
Authors: Sofia R. Gameiro, Momodou L. Jammeh, Max M. Wattenberg, Kwong Y. Tsang, Soldano Ferrone, James W. Hodge
Journal: Cancer Research (2014)

Abstract Radiation therapy (RT) is used for local tumor control through direct killing of tumor cells. Radiation-induced cell death can trigger tumor antigen-specific immune responses, but these are often noncurative. Radiation has been demonstrated to induce immunogenic modulation (IM) in various tumor types by altering the biology of surviving cells to render them more susceptible to T cell-mediated killing. Little is known about the mechanism(s) underlying IM elicited by sub-lethal radiation dosing. We have examined the molecular and immunogenic consequences of radiation exposure in breast, lung, and prostate human carcinoma cells. Radiation induced secretion of ATP and HMGB1 in both dying and surviving tumor cells. In vitro and in vivo tumor irradiation induced significant upregulation of multiple components of the antigen-processing machinery and calreticulin cell-surface expression. Augmented CTL lysis specific for several tumor-associated antigens was largely dictated by the presence of calreticulin on the surface of tumor cells and constituted an adaptive response to endoplasmic reticulum stress, mediated by activation of the unfolded protein response. This study provides evidence that radiation induces a continuum of immunogenic alterations in tumor biology, from immunogenic modulation to immunogenic cell death. We also expand the concept of immunogenic modulation, where surviving tumor cells recovering from radiation-induced endoplasmic reticulum stress become more sensitive to CTL killing. These observations offer a rationale for the combined use of radiation with immunotherapy, including for patients failing RT alone. Citation Format: Sofia R. Gameiro, Momodou L. Jammeh, Max M. Wattenberg, Kwong Y. Tsang, Soldano Ferrone, James W. Hodge. Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 632. doi:10.1158/1538-7445.AM2014-632
THE RECOGNITION AND CLINICAL SIGNIFICANCE OF AURICULAR HEART SOUNDS
Authors: Sidney Scherlis
Journal: Annals of Internal Medicine (1946)

Article1 February 1946THE RECOGNITION AND CLINICAL SIGNIFICANCE OF AURICULAR HEART SOUNDSSIDNEY SCHERLISSIDNEY SCHERLISSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-24-2-254 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe diagnosis of cardiac disease is a clinical problem. Observation and evaluation of the sounds accompanying cardiac activity are of great importance. The electrocardiogram is of value in the analysis of arrhythmias, and is often useful in confirming a clinical diagnosis of myocardial injury. As Levine so aptly stated: "It is a general axiom that the more thoroughly one understands electrocardiography the less one needs it."1 Auscultation of the heart remains a most valuable clinical procedure, not only in the recognition of valvular heart disease, but in identifying arrhythmias as well.The problem of the systolic murmur is a generally...Bibliography1. LEVINE SA: Auscultation of the heart, New England Jr. Med., 1941, ccxxv, 526. CrossrefGoogle Scholar2. LEWIS T: Lectures on the heart, 1914, 53. Google Scholar3. COSSIOFONGI PEG: Auricular sounds, Am. Heart Jr., 1936, xi, 723. CrossrefGoogle Scholar4. FLINT A: On cardiac murmurs, Am. Jr. Med. Sci., 1862, xliv, 29. Google Scholar5. GOULEY BA: The aortic valvular lesion associated with the Austin Flint murmur, Am. Heart Jr., 1941, xxii, 208. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication June 12, 1945.Presented at the meeting of the American Federation for Clinical Research in Boston, Massachusetts on December 9, 1944.The stethographic records upon which this paper is based are from the Department of Medicine, Johns Hopkins Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1946Volume 24, Issue 2Page: 254-258KeywordsArrhythmiaAuscultationCardiovascular therapyElectrocardiographyHeartHeart diseasesHospital medicineSystolic ejection murmur ePublished: 1 December 2008 Issue Published: 1 February 1946 PDF downloadLoading ...
Treatment of mast cells with carbon dioxide suppresses degranulation via a novel mechanism involving repression of increased intracellular calcium levels
Authors: J. W. Strider, C. G. Masterson, P. L. Durham
Journal: Allergy (2010)

Intranasal noninhaled delivery of carbon dioxide (CO₂) is efficacious in the symptomatic treatment of seasonal allergic rhinitis. The goal of this study was to determine whether and how 100% CO₂ inhibits mast cell degranulation, thereby possibly contributing to the reduction of symptoms in seasonal allergic rhinitis. Peritoneal mast cells isolated from rats and labelled with sulforhodamine-B (SFRM-B) were used to determine whether CO₂ treatment could block mast cell degranulation and histamine release in response to 48/80. In addition, the effect of CO₂ on intracellular calcium levels in unstimulated and stimulated mast cells was determined by fluorescent microscopy.Treatment with 48/80 caused >90% of mast cells containing SFRM-B to degranulate, resulting in a marked decrease in the fluorescent intensity within the mast cells, and simultaneously causing a significant increase in histamine release. Significantly, the stimulatory effect of 48/80 on fluorescent intensity and histamine levels was greatly inhibited (>95%) to near control levels by pretreatment with 100% CO₂. Treatment with 48/80 also caused a robust transient increase in intracellular calcium, whereas pretreatment with CO₂ repressed the increase in calcium (>70%) in response to 48/80.Results from this study provide the first evidence of a unique regulatory mechanism by which CO₂ inhibits mast cell degranulation and histamine release by repressing stimulated increases in intracellular calcium. Thus, our data provide a plausible explanation for the reported therapeutic benefit of noninhaled intranasal delivery of 100% CO₂ to treat allergic rhinitis.
Abstract P050: Vitamin K Intake and Risk of Coronary Heart Disease and Stroke in the Rotterdam Study
Authors: Anouk I Engelen, Johanna M Geleijnse, Cees Vermeer, Jacqueline C Witteman, Albert Hofman, Oscar H Franco, Edith J Feskens
Journal: Circulation (2015)

Introduction: Vitamin K serves as a cofactor in the carboxylation of vitamin K-dependent proteins that play a role in blood coagulation and the regulation of vascular calcification. Therefore, vitamin K intake may decrease the risk of cardiovascular diseases (CVD). We aimed to investigate the associations of phylloquinone (vitamin K1) and menaquinone (vitamin K2; MK-4 through MK-10) intake with risk of coronary heart disease (CHD) and stroke in a Dutch population-based cohort study. Methods: The analyses included 4,108 participants of the Rotterdam Study, aged 55 years and older, who were free of CVD and diabetes at baseline. Nutrient intake was estimated using a 170-item semi-quantitative food frequency questionnaire. To estimate the phylloquinone and menaquinone intake we compiled a new vitamin K food composition table using analytical and literature-based values. The occurrence of CHD and stroke was confirmed through medical records. Associations of phylloquinone and menaquinone intake with CHD and stroke incidence were examined using multivariable Cox proportional hazard models. Results: Participants had a mean phylloquinone intake of 191.7 mcg/day and a mean menaquinone intake of 49.4 mcg/day. During follow-up from 1990 to 2011, 460 CHD cases and 546 stroke cases were confirmed. In multivariable-adjusted analyses, we found no associations of phylloquinone (HR: 0.94; 95%CI: 0.72-1.23) or menaquinone intake (0.97; 0.75-1.26) with CHD incidence when comparing the highest to the lowest tertile of intake. Stroke incidence was also not associated with phylloquinone (1.22; 0.96-1.55) or menaquinone intake (0.86; 0.68-1.10). Moreover, we found no associations with CHD or stroke incidence when analysing the intake of short-chain (MK-4 through MK-6) and long-chain menaquinones (MK-7 through MK-10) separately. Conclusion: In this study, phylloquinone and menaquinone intake were not associated with risk of CHD or stroke.
Periodontal disease in HIV/AIDS
Authors: Mark I. Ryder, Wipawee Nittayananta, Maeve Coogan, Deborah Greenspan, John S. Greenspan
Journal: Periodontology 2000 (2012)

Abstract Since the early 1990's, the death rate from AIDS among adults has declined in most developed countries, largely because of newer antiretroviral therapies and improved access to these therapies. In addition, from 2006 to 2011, the total number of new cases of HIV infection worldwide has declined somewhat and has remained relatively constant. Nevertheless, because of the large numbers of existing and new cases of HIV infection, the dental practitioner and other healthcare practitioners will still be required to treat oral and periodontal conditions unique to HIV/AIDS as well as conventional periodontal diseases in HIV‐infected adults and children. The oral and periodontal conditions most closely associated with HIV infection include oral candidiasis, oral hairy leukoplakia, Kaposi’s sarcoma, salivary gland diseases, oral warts, other oral viral infections, linear gingival erythema and necrotizing gingival and periodontal diseases. While the incidence and prevalence of these oral lesions and conditions appear to be declining, in part because of antiretroviral therapy, dental and healthcare practitioners will need to continue to diagnose and treat the more conventional periodontal diseases in these HIV‐infected populations. Finding low‐cost and easily accessible and acceptable diagnostic and treatment approaches for both the microbiological and the inflammatory aspects of periodontal diseases in these populations are of particular importance, as the systemic spread of the local microbiota and inflammatory products of periodontal diseases may have adverse effects on both the progression of HIV infection and the effectiveness of antiretroviral therapy approaches. Developing and assessing low‐cost and accessible diagnostic and treatment approaches to periodontal diseases, particularly in developing countries, will require an internationally coordinated effort to design and conduct standardized clinical trials.
Abstract P2-06-03: Prostaglandin E receptor EP4 is a therapeutic target in breast cancer stem cells
Authors: Amy Fulton, Namita Kundu, Tyler Kochel, Xinrong Ma, Jocelyn Reader
Journal: Cancer Research (2015)

Abstract There is an urgent need to identify mechanisms underlying the survival of cells expressing cancer stem cell or tumor-initiating properties. The cyclooxygenase-2 (COX-2) pathway is highly expressed in many breast tumors and contributes to poor outcomes. The COX-2 product prostaglandin E2 (PGE2) promotes tumor growth and metastasis by acting on the G-protein-coupled receptor EP4. We compared the expression and function of COX-2 and EP4 in mammosphere-forming and bulk populations derived from a panel of human and murine luminal and basal type tumor cells with different metastatic capacities. Expression of both EP4 and COX-2 were markedly increased in mammosphere-forming cells derived from basal and/or metastatic cells relative to the bulk population, but neither COX-2 or EP4 levels were elevated in mammospheres derived from luminal or non-metastatic cells. Breast cancer stem cells, expressing elevated EP4 are correspondingly more sensitive to inhibition with EP4 antagonists both in vitro and in limiting-dilution assays in vivo. Somewhat to our surprise, cancer stem cells remain relatively sensitive to lysis by Natural Killer cells. We have also shown that EP4 blockade protects NK cells from tumor-induced immune suppression. These studies identify EP4 as a potential therapeutic target in the general tumor cell population and show that EP4 targeting may selectively inhibit cells with tumor-initiating or stem cell properties. EP4 antagonists can directly inhibit cancer stem cells and tumor metastasis and indirectly support NK-mediated mechanisms of tumor control. We are delineating the mechanisms by which EP4 and COX-2 are upregulated in cells with stem-like properties. In addition to EP4 and COX-2, STAT3 is upregulated in stem cells. Inhibition of STAT3 reduces mammosphere-forming capacity. Our studies support a mechanism whereby COX-2/EP4 signaling induces STAT3 to support breast cancer stem cell survival by a feed-forward mechanism. Citation Format: Amy Fulton, Namita Kundu, Tyler Kochel, Xinrong Ma, Jocelyn Reader. Prostaglandin E receptor EP4 is a therapeutic target in breast cancer stem cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-03.
Potential value of an ELISPOT interferon gamma release assay as a diagnostic tool in Q fever infection
Authors: Gijs Limonard, John Bouwman, Anita Asscheman, Steven Thijsen, Bart Vlaminckx, Aik Bossink
Journal: European Respiratory Journal (2011)

Rationale:  Q fever is an emerging zoonosis in the Netherlands, atypical pneumonia being the most common clinical manifestation. Acute disease is followed by resolution in the majority of cases, 10-20% will exhibit the post-Q fever fatigue syndrome (QFS) and 1-5% of patients progresses to chronic disease. Current tests measuring humoral immune response to Coxiella burnetii have considerable limitations in diagnosing these different outcomes. We conducted an exploratory study to determine T cell response to C. burnetii specific antigens using an ELISPOT interferon gamma release assay (Coxiella ELISPOT).   Methods:  An in-house developed Coxiella ELISPOT interferon gamma release assay, using both phase I and phase II antigens was performed on blood samples of Q fever patients.   Results:  Coxiella ELISPOT was performed for 7 patients reconvalesced after acute Q fever and 2 chronic Q fever patients (n=1 newly diagnosed, n=1 after completion of treatment). Mean (± SE) spot count for reconvalesced patients was 11±5 (range 1-42) for phase I and 31±15 (range 1-120) for phase II. One patient was diagnosed with QFS and had the highest spot count in both phase I (42 spots) and phase II (120 spots). The newly diagnosed chronic Q fever patient (male, 64 ys) showed a predominant responsiveness to phase I antigen (spot count Phase I 209, Phase II 177). The other chronic Q fever patient (male, 67 ys) had finished a 18 month antibiotic treatment for Q fever endocarditis. Coxiella ELISPOT showed a marked T cell unresponsiveness to both phase I (3 spots) and phase II antigens (0 spots).   Conclusion:  Different clinical Q fever outcomes are associated with marked differences in Coxiella ELISPOT results.
DIABETES TODAY AND TOMORROW
Authors: Elliott P. Joslin
Journal: Annals of Internal Medicine (1936)

Article1 August 1936DIABETES TODAY AND TOMORROWELLIOTT P. JOSLIN, M.D., F.A.C.P.ELLIOTT P. JOSLIN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-10-2-179 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe Hagedorn Era. Today we are standing on the threshold of a new era in diabetes. The Banting Era which we are now leaving was wonderful, and, even more, it was awe-inspiring. During these last 14 years you and I have seen diabetics gain hope, food, strength; insulin has breathed life into their dry bones and they stand upon their feet, a mighty army. Yet complications, although lessened in number and severity, persist and—I almost blush to admit it—diabetic coma is allowed to prowl about and decimate our diabetics by seizing the innocent, because undiagnosed, the ignorant and the careless.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ELLIOTT P. JOSLIN, M.D., F.A.C.P.Affiliations: Boston, Massachusetts*Presented at the Detroit meeting of the American College of Physicians, March 2, 1936. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1936Volume 10, Issue 2Page: 179-193KeywordsBoneComaFoodInsulin ePublished: 1 December 2008 Issue Published: 1 August 1936 PDF downloadLoading ...