tbuckley/cabot-search huggingface dataset:
Dose-related effects of formoterol on airway responsiveness to adenosine 5′‐monophosphate and histamine
Authors: R.I. Ketchell, M.W. Jensen, D. Spina, B.J. O'Connor
Journal: European Respiratory Journal (2002)

Inhaled short-acting β 2 ‐agonists provide greater protection against airway responsiveness (AR) to the mast-cell stimulus, adenosine 5′‐monophosphate (AMP), than to histamine, a direct spasmogen. Both terbutaline and albuterol exhibit this mast-cell stabilizing property in a dose-dependent manner. A single dose of the long-acting β 2 ‐agonist formoterol has also been reported to have a mast cell-stabilizing effect, whereas salmeterol has not. To explore the dose-related actions of the long-acting β 2 ‐agonist formoterol on AR, the authors compared the acute effects of three doses of formoterol and terbutaline on AR to AMP and histamine. In a double-blind, randomized, placebo-controlled, cross-over study, 25 mild, steroid naive, asthmatic subjects attended on 10 occasions. At each visit, subjects inhaled either a single dose of terbutaline (500 µg), formoterol (6, 12 or 24 µg) or a matched placebo, administered via Turbuhaler®, 30 min prior to challenge with both AMP and histamine. Each dose of β 2 ‐agonist reduced AR to AMP and histamine. The bronchoprotective effects of formoterol (6 µg) and terbutaline (500 µg) were similar in magnitude in reducing AR to histamine (mean±sd: 3.6±0.3 and 3.1±0.3 doubling doses (DD)) and AR to AMP (3.5±0.5 and 3.3±0.4 DD, respectively). Overall, formoterol reduced AR to both spasmogens in a dose-dependent manner. In addition, formoterol (12 and 24 µg) provided a significantly greater protective effect against AMP than against histamine challenge. It decreased AR by 5.7±0.6 and 6.3±0.7 DD against AMP and 4.3±0.4 and 4.8±0.43 DD against histamine, respectively. The results of this study indirectly demonstrated an in vivo dose-dependent mast-cell stabilizing effect of formoterol, in addition to functional antagonism on airway smooth muscle. This property of β 2 ‐agonists may have clinical benefits in asthma management.
Long-Term Disease-Specific Functioning Among Prostate Cancer Survivors and Noncancer Controls in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Kathryn L. Taylor, George Luta, Anthony B. Miller, Timothy R. Church, Scott P. Kelly, Larry R. Muenz, Kimberly M. Davis, David L. Dawson, Sara Edmond, Douglas Reding, Jerome E. Mabie, Thomas L. Riley
Journal: Journal of Clinical Oncology (2012)

Purpose Within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), we assessed the long-term disease-specific functioning among prostate cancer (PCa) survivors versus noncancer controls, the impact of trial arm (screening/usual care) on functioning, and the effect of treatment modality on functioning. Patients and Methods PCa survivors (n = 529), 5 to 10 years postdiagnosis, were frequency-matched to noncancer controls (n = 514) for race, screening center, year of enrollment, and trial arm. Participants completed a telephone interview regarding PCa-specific symptomatology. Weights accounted for patient selection from the five PLCO screening centers. Propensity-score methods were used to balance groups of interest with respect to demographic and medical characteristics. Results Weighted linear regression analyses revealed poorer sexual and urinary function among PCa survivors compared with noncancer controls (P &lt; .001). Trial arm was not significantly related to any outcome (P &gt; .31). Compared with radical prostatectomy patients (n = 201), radiation-therapy patients (n = 110) reported better sexual (P &lt; .05) and urinary (P &lt; .001) functioning but poorer bowel outcomes (P &lt; .05). Survivors who received treatment combinations including androgen deprivation (n = 207) reported significantly poorer hormone-related symptoms compared with radical prostatectomy patients (P &lt; .05). Conclusion This study demonstrated the persistence of clinically significant, long-term PCa treatment-related sexual and urinary adverse effects up to 10 years postdiagnosis. To our knowledge, this was the first comparison of prostate-related dysfunction among screened survivors versus screened noncancer controls and indicated that these long-term problems were attributable to PCa treatment and not to aging or comorbidities. Finally, differences in long-term adverse effects between treatment modalities are particularly relevant for patients and clinicians when making treatment decisions.
Flow patterns and spatial distribution of atherosclerotic lesions in human coronary arteries.
Authors: T Asakura, T Karino
Journal: Circulation Research (1990)

To investigate the potential role of fluid mechanical factors in the localized genesis and development of atherosclerotic lesions in humans, the exact anatomic locations of atherosclerotic lesions and the flow patterns at such sites in left and right human coronary arteries were studied in detail by flow visualization and high-speed cinemicrographic techniques using five isolated, transparent human coronary arterial trees prepared postmortem. It was found that atherosclerotic plaques and wall thickenings in left and right coronary arteries were localized almost exclusively on the outer wall of one or both daughter vessels at major bifurcations and T-junctions, which left the flow-divider free of lesions, and along the inner wall of curved segments. When flow patterns in such vessels were studied in detail, it was discovered that these sites were where flow was either slow or disturbed with the formation of slow recirculation and secondary flows and where wall shear stress was low. The results indicate that the major hemodynamic factors directly related to the localization of atherosclerotic plaques and wall thickenings in the human arterial system are the low fluid velocity and the resultant low shear stress that acts on the vessel wall.
Mortality from methicillin resistant Staphylococcus aureus
Authors: A. J Howard
Journal: BMJ (2003)

Media influence on suicide Television programme makers have an ethical responsibilityEditor-We agree with Hawton and Williams that training courses for careers in the media offer the potential for improved portrayal of suicide in the media. 1 The media, however, clearly can affect many facets of health related behaviour.We recently reported the effect of the death from cervical cancer of a character (Alma) in the television soap opera Coronation Street on the NHS cervical screening programme in the north west of England. 2 3 Our studies showed an excess of 14 000 cervical smear tests performed as a result of the storyline (a 21% increase on the previous year), although only 2000 of them were in women whose test was overdue or who had had no previous smear test.The remaining 12 000 smear tests were performed on women attending for an early, unscheduled test or who were due a smear test anyway and brought their appointment forward.The large increase in the number of smear tests led to a strain on local laboratories, with the time taken to report results increasing to beyond acceptable quality assurance limits-a factor likely to provoke excess anxiety in women.We also found that many women were prompted to attend for a cervical smear test because the storyline made them worry.This anxiety generating approach contrasts with current initiatives to encourage women to make an informed choice about screening.Television programme makers should realise the power of such stories not only to achieve maximal viewing figures but also to cause fear and anxiety, as well as the consumption of scarce healthcare resources.Those responsible for promoting health need to engage programme makers in a full ethical debate.
RELATIONSHIP BETWEEN URINARY HYDROXYPROLINE AND GROWTH*
Authors: H. E. Jasin, C. W. Fink, W. Wisf, M. Ziff
Journal: Journal of Clinical Investigation (1962)

Beginning with the report of Ziff, Kibrick, Dresner, and Gribetz (2), evidence accumulated in recent years has indicated that urinary hydroxyproline excretion reflects collagen metabolism, since collagen is the only protein in the body that contains hydroxyproline in significant amounts (3).Ziff and co-workers, observing that the excretion of this amino acid in peptide form was greater in children than in adults, suggested that the level of urinary hydroxyproline might be re- lated to the size of the metabolically active, solu- ble collagen pool available for breakdown.The results of a number of investigations (4-7) have supported this suggestion.In the present paper, further investigation of the relationship between growth and hydroxypro- line excretion has been carried out in man.Uri- nary hydroxyproline has been determined in pa- tients with normal, arrested, and accelerated growth, and in cases in which arrested growth has been stimulated by hormonal therapy.The data obtained indicate that the level of excretion of hydroxyproline shows a good correlation with rate of growth under all circumstances studied and, therefore, offers a useful and readily meas- ured index of this phenomenon. METHODS AND MATERIALSNormal controls.Urines from normal children and adults were collected at home.In the 0-to 1-year group, the urine was collected in absorbent diapers with a special tissue paper sheet to isolate the feces.Diapers were changed six times in 24 hours.Upon removal, they were immersed in water saturated with toluene, and at the end of a 24-hour collection period, centrifuged in * Work
Development, validity and reliability of the food allergy independent measure (FAIM)
Authors: J. L. Van Der Velde, B. M. J. Flokstra‐de Blok, B. J. Vlieg‐Boerstra, J. N. G. Oude Elberink, A. DunnGalvin, J. O’B. Hourihane, E. J. Duiverman, A. E. J. Dubois
Journal: Allergy (2009)

The Food Allergy Quality of Life Questionnaire-Child Form, -Teenager Form and -Adult Form (FAQLQ-CF, -TF and -AF) have recently been developed. To measure construct validity in the FAQLQs, a suitable independent measure was needed with which FAQLQ scores could be correlated. However, in food allergy, no appropriate independent measure existed, which could be used for this purpose.The aim of this study was to describe the development of a Food Allergy Independent Measure Child-Form, -Teenager Form and -Adult Form (FAIM-CF, -TF and -AF) and to assess their validity and reliability.The FAIMs were developed using previously established methodology to capture the patients' expectation of outcome (EO). Face validity was determined by expert opinion. FAIM questions showing no correlation to any potential items in the FAQLQs were considered irrelevant and eliminated. To measure test-retest reliability, one-hundred and one patients were included and completed the FAIM twice with a 10-14 day interval. The intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC) and Bland-Altman plots were used to assess test-retest reliability.Six FAIM questions were developed and considered relevant for the FAIM-CF and -AF, and five questions were relevant for the FAIM-TF. The FAIMs showed good reliability with ICCs and CCCs above 0.70 and with mean differences all close to zero.Food allergy independent measures were developed for children, adolescents and adults and were shown to be valid, relevant and reliable. This supports the suitability of the FAIMs for evaluating construct validity.
Randomized Phase II Placebo-Controlled Trial of Maintenance Therapy Using the Oral Triple Angiokinase Inhibitor BIBF 1120 After Chemotherapy for Relapsed Ovarian Cancer
Authors: Jonathan A. Ledermann, Allan Hackshaw, Stan Kaye, Gordon Jayson, Hani Gabra, Iain McNeish, Helena Earl, Tim Perren, Martin Gore, Mojca Persic, Malcolm Adams, Lindsay James, Graham Temple, Michael Merger, Gordon Rustin
Journal: Journal of Clinical Oncology (2011)

Purpose Inhibiting angiogenesis is one of the most promising avenues for new therapies for ovarian cancer. We investigated the efficacy and safety of a novel agent, BIBF 1120, a triple angiokinase inhibitor, after chemotherapy for relapsed disease. Patients and Methods We conducted a randomized, double-blind, controlled phase II trial in 83 patients who had just completed chemotherapy for relapsed ovarian cancer, with evidence of response, but at high risk of further early recurrence. The patients were randomly assigned to receive maintenance therapy using BIBF 1120 250 mg or placebo, twice per day, continuously for 36 weeks. End points were progression-free survival (PFS), toxicity, and overall survival. Results Thirty-six–week PFS rates were 16.3% and 5.0% in the BIBF 1120 and placebo groups, respectively (hazard ratio, 0.65; 95% CI, 0.42 to 1.02; P = .06). Four patients continued on BIBF 1120, including two patients for another year or more. The proportion of patients with any grade 3 or 4 adverse events was similar between the groups (34.9% for BIBF 1120 v 27.5% for placebo; P = .49; mostly grade 3). However, more patients on BIBF 1120 experienced diarrhea, nausea, or vomiting (mainly grade 1 or 2 and no grade 4). There was a higher rate of grade 3 or 4 hepatotoxicity in patients on BIBF 1120 (51.2%) compared with patients on placebo (7.5%; P &lt; .001), but this was rarely of clinical significance, and patients continued with the trial treatment. A single-level dose reduction to 150 mg was made in 15 patients, all on active drug. Conclusion BIBF 1120 is well tolerated and associated with a potential improvement in PFS. The observed treatment effect is sufficient to justify further study within a large phase III trial.
Integrin subunits alpha5 and alpha6 regulate cell cycle by modulating the chk1 and Rb/E2F pathways to affect breast cancer metastasis
Authors: Yanfang Wang, Sylvia Shenouda, Somesh Baranwal, Rajamani Rathinam, Prachi Jain, Lili Bao, Siddhartha Hazari, Srikanta Dash, Suresh K Alahari
Journal: Molecular Cancer (2011)

Although integrins have been implicated in the progression of breast cancer, the exact mechanism whereby they exert this regulation is clearly not understood. To understand the role of integrins in breast cancer, we examined the expression levels of several integrins in mouse breast cancer cell lines by flow cytometry and the data were validated by Western and RT-PCR analysis. The importance of integrins in cell migration and cell invasion was examined by in vitro assays. Further the effect of integrins on metastasis was investigated by in vivo experimental metastasis assays using mouse models.Integrin α5 subunit is highly expressed in the nonmetastatic cell line 67NR and is significantly low in the highly invasive cell line 4T1. In contrast, expression levels of integrin α6 subunit are high in 4T1 cells and low in 67NR cells. In vitro data indicated that overexpression of α5 subunit and knockdown of α6 integrin subunit inhibited cell proliferation, migration, and invasion. Our in vivo findings indicated that overexpression of integrin α5 subunit and knockdown of α6 subunit decreased the pulmonary metastasis property of 4T1 cells. Our data also indicated that overexpression of alpha 5 integrin subunit and suppression of alpha6 integrin subunit inhibited cells entering into S phase by up-regulating p27, which results in downregulation of cyclinE/CDK2 complexes, This suggests that these integrins regulate cell growth through their effects on cell-cycle-regulated proteins. We also found that modulation of these integrins upregulates E2F, which may induce the expression of chk1 to regulate cdc25A/cyclin E/CDK2/Rb in a feedback loop mechanism.This study indicates that Integrin α5 subunit functions as a potential metastasis suppressor, while α6 subunit functions as a metastasis promoter. The modulation of integrins reduces cdc25 A, another possible mechanism for downregulation of CDK2. Taken together we demonstrate a link between integrins and the chk1-cdc25-cyclin E/CDK2-Rb pathway.
Hepatocytes as a source of cholangiocytes in injured liver
Authors: Frédéric P. Lemaigre
Journal: Hepatology (2013)

Abstract Cellular reprogramming—the ability to interconvert distinct cell types with defined factors—is transforming the field of regenerative medicine. However, this phenomenon has rarely been observed in vivo without exogenous factors. Here, we report that activation of Notch, a signaling pathway that mediates lineage segregation during liver development, is sufficient to reprogram hepatocytes into biliary epithelial cells (BECs). Moreover, using lineage tracing, we show that hepatocytes undergo widespread hepatocyte-to-BEC reprogramming following injuries that provoke a biliary response, a process requiring Notch. These results provide direct evidence that mammalian regeneration prompts extensive and dramatic changes in cellular identity under injury conditions.
Role of ADAMs in Cancer Formation and Progression
Authors: Michael J. Duffy, Eadaoin McKiernan, Norma O'Donovan, Patricia M. McGowan
Journal: Clinical Cancer Research (2009)

Abstract The ADAMs (a disintegrin and metalloproteinase) comprise a family of multidomain transmembrane and secreted proteins. One of their best-established roles is the release of biologically important ligands, such as tumor necrosis factor–α, epidermal growth factor, transforming growth factor–α, and amphiregulin. Because these ligands have been implicated in the formation and progression of tumors, it might be expected that the specific ADAMs involved in their release would also be involved in malignancy. Consistent with this hypothesis, emerging data from model systems suggest that ADAMs, such as ADAM-9, ADAM-12, ADAM-15, and ADAM-17, are causally involved in tumor formation/progression. In human cancer, specific ADAMs are up-regulated, with levels generally correlating with parameters of tumor progression and poor outcome. In preclinical models, selective ADAM inhibitors against ADAM-10 and ADAM-17 have been shown to synergize with existing therapies in decreasing tumor growth. The ADAMs are thus a new family of potential targets for the treatment of cancer, especially malignancies that are dependent on human epidermal growth factor receptor ligands or tumor necrosis factor–α.
Imatinib Suppresses Cryoglobulinemia and Secondary Membranoproliferative Glomerulonephritis
Authors: Masayuki Iyoda, Kelly L. Hudkins, Shirly Becker-Herman, Tomasz A. Wietecha, Miriam C. Banas, Shunhua Guo, Almut Meyer-Bahlburg, Jolanta Kowalewska, Gang Liu, Steven F. Ziegler, David J. Rawlings, Charles E. Alpers
Journal: Journal of the American Society of Nephrology (2008)

Imatinib is a receptor tyrosine kinase inhibitor that blocks the activity of c-Abl, c-Kit, and PDGF receptors. We tested the protective effects of imatinib in thymic stromal lymphopoietin transgenic mice, a model of cryoglobulinemia and associated membranoproliferative glomerulonephritis (MPGN), in which some glomerular manifestations likely result from PDGF receptor activation. Surprising, administration of imatinib beginning at weaning suppressed production of cryoglobulin, attenuating both the renal injury and systemic features of cryoglobulinemia. Flow cytometry suggested that inhibition of B cell development in the bone marrow likely caused the reduction in cryoglobulin production. In addition, administration of imatinib to thymic stromal lymphopoietin transgenic mice with established MPGN also diminished cryoglobulin production and reversed the renal and systemic lesions. These data suggest that treatment with imatinib may be a novel therapeutic approach for cryoglobulinemia and MPGN in humans.
Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion
Authors: T Sudhop
Journal: Gut (2002)

<b>Background:</b> Recently identified ABCG5/8 transporters are responsible in part for the different absorption rates of campesterol, sitosterol, and cholesterol. These transporters are also expressed in the liver and might regulate biliary sterol secretion. <b>Aims:</b> This study was therefore conducted to determine the biliary secretion rates and hepatic clearances of campesterol, sitosterol, and cholesterol. <b>Subjects:</b> Six healthy, male volunteers. <b>Methods:</b> Deuterium labelled sitosterol and campesterol, and unlabelled sitostanol were constantly infused together with a liquid formula using a duodenal perfusion technique. Biliary secretion and hepatic clearance rates were calculated from hourly bile and plasma samples. <b>Results:</b> Plasma concentrations of cholesterol, campesterol, and sitosterol averaged 167.5 (50) mg/dl (SD), 0.50 (0.22) mg/dl, and 0.30 (0.10) mg/dl, respectively. Sitosterol showed a significantly higher biliary secretion rate (1.23 (0.87) mg/h) than campesterol (0.76 (0.54) mg/h, p=0.0321), but both plant sterols had significantly lower biliary secretion rates compared with cholesterol (47.7 (17.5) mg/h; p=0.001 for both). Hepatic clearance of cholesterol (0.31 (0.18) dl/h) was significantly lower compared with campesterol (2.11 (2.51) dl/h) and sitosterol (4.97 (4.70) dl/h; p=0.028 for both), and the clearance of campesterol was significant lower compared with sitosterol (p=0.028). <b>Conclusion:</b> The observed inverse relation between hepatic clearance and known intestinal absorption of cholesterol, campesterol, and sitosterol supports the hypothesis that the ABCG5/8 transporters regulating intestinal sterol absorption might also be involved in biliary sterol excretion.
STUDIES ON THE PATHOGENESIS OF RABIES IN INSECTIVOROUS BATS
Authors: S. Edward Sulkin, Rae Allen, Ruth Sims, Philip H. Krutzsch, Chansoo Kim
Journal: The Journal of Experimental Medicine (1960)

Studies on the influence of environmental temperature on the pathogenesis of rabies in two species of experimentally infected Chiroptera, the Mexican free-tailed bat (Tadarida mexicana) and the little brown bat (Myotis lucifugus), provided evidence that little or no viral multiplication occurs in the inactive host during experimentally induced hibernation. When inoculated animals are wakened from hibernation by transfer to a warm room, virus previously in "cold storage" multiplies, reaching detectable levels in various tissues. Similar results were obtained with two strains of rabies virus, a canine rabies street virus which produced a fatal infection in man and a strain isolated from the pooled brown fat of naturally infected little brown bats. However, certain differences in the characteristics of these virus strains were observed. The canine rabies virus strain produced an encephalitic disease in mice and overt symptoms in bats; the bat rabies virus producing an encephalomyelitic disease in mice and infrequent symptoms in bats. The bat rabies virus had a greater predilection for brown adipose tissue than the canine strain. Results obtained with the bat rabies virus in hibernating animals indicate that after a period of latency in a dormant animal activated virus may reach the salivary gland more rapidly, with greater frequency, and attain higher concentrations than in animals which have not experienced a period of hibernation. The significance of these results as they relate to the natural history of bat rabies is discussed.