tbuckley/cabot-search huggingface dataset:
Effects of inhaled fluticasone and oral prednisolone on clinical and inflammatory parameters in patients with asthma
Authors: R J Meijer, H A M Kerstjens, L R Arends, H F Kauffman, G H Koeter, D S Postma
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Guidelines state that oral and inhaled corticosteroids are the cornerstone of asthma treatment. The effect of both types of treatment can be assessed by measuring lung and systemic parameters. Treatment for two weeks with either oral prednisolone (30 mg/day), high dose fluticasone propionate (2000 μg/day, FP2000), or lower dose FP (500 μg/day, FP500), both given by a dry powder inhaler, were compared. <h3>METHODS</h3> One hundred and twenty patients with asthma were treated for two weeks in a double blind parallel group design. Lung function, asthma symptoms, airway hyperresponsiveness (PC<sub>20</sub> methacholine and adenosine-5′-monophosphate), sputum eosinophil and eosinophilic cationic protein (ECP) levels were measured as lung parameters. In addition, morning serum blood cortisol, blood eosinophil, and serum ECP levels were measured as systemic parameters. <h3>RESULTS</h3> PC<sub>20</sub>methacholine and adenosine-5′-monophosphate showed significantly greater improvement with FP2000 (1.99 and 4.04 doubling concentrations (DC), respectively) than prednisolone (0.90 DC, p = 0.02; 2.15 DC, p = 0.05) and marginally more than with FP500 (1.69 and 3.54 DC). Changes in sputum eosinophil and ECP concentrations showed similar trends; the decrease in ECP was significantly greater with FP2000 than with FP500. In contrast, the systemic parameters of steroid activity (cortisol, peripheral blood eosinophils, and serum ECP) decreased to a similar extent with FP2000 and prednisolone but significantly less with FP500. <h3>CONCLUSIONS</h3> Oral prednisolone (30 mg/day) was inferior to FP2000 in improving airway hyperresponsiveness to both methacholine and AMP, with similar trends in forced expiratory volume in one second (FEV<sub>1</sub>), sputum eosinophil and ECP concentrations. Systemic effects were similar with prednisolone and FP2000 and less with FP500.
Cardiomyocyte GTP Cyclohydrolase 1 and Tetrahydrobiopterin Increase NOS1 Activity and Accelerate Myocardial Relaxation
Authors: Ricardo Carnicer, Ashley B. Hale, Silvia Suffredini, Xing Liu, Svetlana Reilly, Mei Hua Zhang, Nicoletta C. Surdo, Jennifer K. Bendall, Mark J. Crabtree, Gregory B.S. Lim, Nicholas J. Alp, Keith M. Channon, Barbara Casadei
Journal: Circulation Research (2012)

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthases (NOS). Oral BH4 supplementation preserves cardiac function in animal models of cardiac disease; however, the mechanisms underlying these findings are not completely understood.To study the effect of myocardial transgenic overexpression of the rate-limiting enzyme in BH4 biosynthesis, GTP cyclohydrolase 1 (GCH1), on NOS activity, myocardial function, and Ca2+ handling.GCH1overexpression significantly increased the biopterins level in left ventricular (LV) myocytes but not in the nonmyocyte component of the LV myocardium or in plasma. The ratio between BH4 and its oxidized products was lower in mGCH1-Tg, indicating that a large proportion of the myocardial biopterin pool was oxidized; nevertheless, myocardial NOS1 activity was increased in mGCH1-Tg, and superoxide release was significantly reduced. Isolated hearts and field-stimulated LV myocytes (3 Hz, 35°C) overexpressing GCH1 showed a faster relaxation and a PKA-mediated increase in the PLB Ser16 phosphorylated fraction and in the rate of decay of the [Ca2+]i transient. RyR2 S-nitrosylation and diastolic Ca2+ leak were larger in mGCH1-Tg and ICa density was lower; nevertheless the amplitude of the [Ca2+]i transient and contraction did not differ between genotypes, because of an increase in the SR fractional release of Ca2+ in mGCH1-Tg myocytes. Xanthine oxidoreductase inhibition abolished the difference in superoxide production but did not affect myocardial function in either group. By contrast, NOS1 inhibition abolished the differences in ICa density, Ser16 PLB phosphorylation, [Ca2+]i decay, and myocardial relaxation between genotypes.Myocardial GCH1 activity and intracellular BH4 are a limiting factor for constitutive NOS1 and SERCA2A activity in the healthy myocardium. Our findings suggest that GCH1 may be a valuable target for the treatment of LV diastolic dysfunction.
Cytoskeletal features of rat aortic cells during development. An electron microscopic, immunohistochemical, and biochemical study.
Authors: O Kocher, O Skalli, D Cerutti, F Gabbiani, G Gabbiani
Journal: Circulation Research (1985)

Actin, vimentin, desmin, and tropomyosin distribution in rat aortic endothelial and smooth muscle cells has been studied during development using fetal (18 to 20 days of gestation), and 5- and 14-day-, and 5-, and 12-week-old rats. Endothelial cells of newborn animals actively replicate and contain many actin stress fibers, whereas, in adult animals, replication is minimal and actin stress fibers are rare. The actin, vimentin, desmin, and tropomyosin content of smooth muscle cells increases gradually from fetal to adult animals. The number of desmin-containing cells also increases from 13% in fetal rats to 51% in adult rats. The beta-actin isoform is predominant in fetal and newborn animals, but gradually the alpha-isoform becomes quantitatively the most important, as seen by bidimensional polyacrylamide gels. Several analogies exist between the features of developing smooth muscle and what is known for developing striated muscle cells. The evolution of cytoskeletal features from fetal to adult animals is remarkably the opposite of what takes place in: (1) rat aortic smooth muscle cells proliferating after an endothelial injury, (2) human arterial smooth muscle cells present in atheromas, and (3) actively growing rat aortic smooth muscle cells in vitro. Thus, the assumption that pathological or cultured smooth muscle cells are "dedifferentiated" is supported by our biochemical observations.
Pulmonary arteriovenous fistula presenting as spontaneous haemothorax.
Authors: B S Spear, L Sully, T Lewis
Journal: Thorax (1975)

We record a case of pulmonary arteriovenous fistula presenting in a dramatic and unusual way. These lesions are generally diagnosed clinically by consideration of their associated features. In this case these were all absent, and the patient presented with a spontaneous haemothorax as an isolated finding. When blood is found on aspiration of the pleural cavity it generally represents bloodstained effusion (trauma excluded), and by far the commonest cause is bronchogenic carcinoma. Less frequently, however, aspiration of blood may represent spontaneous intrapleural bleeding without effusion (spontaneous haemothorax), and a rare cause of this situation is pulmonary arteriovenous fistula. We record this case to demonstrate that innocent pulmonary arteriovenous fistulae can masquerade as carcinoma.
Structure, Promoter Analysis, and Chromosomal Localization of the Murine H+/K+-ATPase α2 Subunit Gene
Authors: Wenzheng Zhang, Teresa Kuncewicz, Sandra C. Higham, Bruce C. Kone
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. The H+/K+-ATPase α2 subunit (HKα2) of distal colon and renal collecting ducts plays a critical role in potassium and acid-base homeostasis. The isolation and complete sequence of the murine HKα2 gene are reported. The HKα2 gene contains 23 exons and spans 23.5 kb of genomic DNA. The exon/intron organization is comparable to that of the human ATP1AL1 gene. Primer extension and 5′-rapid amplification of cDNA ends of distal colon RNA were used to map the transcription initiation site. Fluorescence in situ hybridization analysis localized the HKα2 gene to murine chromosome 14C3. Sequence analysis of 7.2 kb of the 5′-flanking region revealed numerous consensus sites for transcription factors, including two potential glucocorticoid response elements. Transient transfection of promoter-luciferase constructs demonstrated strong basal HKα2 promoter activity in renal collecting duct cells but not in fibroblasts or in a medullary thick ascending limb of Henle's loop cell line. Deletion analysis revealed that the proximal 0.2 kb of the promoter was sufficient to confer activity in collecting duct cells. These data should prove important in elucidation of the mechanisms controlling the differential, tissue-specific expression of the HKα2 gene.
Does Active Rescuer Ventilation Have a Place During Basic Cardiopulmonary Resuscitation?
Authors: Petter Andreas Steen
Journal: Circulation (2007)

R escuer ventilation has always been an integral part of both basic (BLS) and advanced (ACLS) cardiac life support. 1Despite 5 decades of continuous attempts to improve training in cardiopulmonary resuscitation (CPR), maintenance of free airways and adequate ventilation continue to be difficult skills to acquire and maintain for both lay persons and professionals.Because of airway problems and excessive inflation pressures, much of the air enters the stomach instead of the lungs during bystander CPR, 2 and in a recent study, 39% of patients receiving mouth-to-mouth ventilation had signs of regurgitation at the time of intubation.
Hemodynamic Changes in Hypophysectomized Rats
Authors: MARGARET BEZNÁK
Journal: Circulation Research (1959)

The following changes were observed in hypophysectomized rats, 14 days after the operation: greatly reduced cardiac output, bradycardia, slight increase in total peripheral resistance, less work done by the left ventricle, low blood pressure, reduced respiratory rate and oxygen uptake, no change in blood volume and erythrocyte count. During an increased input or resistance load, the output and work of the heart rose greatly both in normal and in hypophysectomized rats. The maximum work which the heart did under these conditions, especially if the size of the heart was taken into consideration, was not significantly less in hypophysectomized than in normal rats. It is concluded that the low cardiac output after hypophysectomy is not primarily of cardiac origin.
Shortened First-Line High-Dose Chemotherapy for Patients With Poor-Prognosis Aggressive Lymphoma
Authors: Christian Gisselbrecht, Eric Lepage, Thierry Molina, Bruno Quesnel, Georges Fillet, Pierre Lederlin, Bertrand Coiffier, Hervé Tilly, Jean Gabarre, Francoise Guilmin, Olivier Hermine, Félix Reyes
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Randomized trial LNH93-3 was conducted on patients who had poor-prognosis aggressive lymphoma and were younger than 60 years with two to three factors of the age-adjusted International Prognostic Index to evaluate the benefit of early high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Patients were randomized between doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) chemotherapy followed by sequential consolidation and an experimental shortened treatment consisting of three cycles with escalated doses of cyclophosphamide, epirubicin, vindesine, bleomycin, and prednisone and collection of peripheral-blood stem cells. On day 60, HDT was administered with 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, cytarabine, and melphalan followed by ASCT. RESULTS: Eligible patients (n = 370) with aggressive lymphoma were analyzed. For ACVBP (181 patients) and HDT (189 patients), respective complete remission rates were 64% and 63%. With a median follow-up of 60 months, 5-year overall survival and event-free survival for ACVBP and HDT were 60% ± 8% and 46% ± 8% (P = .007) and 52 ± 8% and 39 ± 8% (P = .01), respectively. Survival was independently affected by age greater than 40 years (P = .0003), T-cell phenotype (P = .009), bone marrow involvement (P = .003), and HDT treatment group (P = .04). CONCLUSION: Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy regimen. These results indicate that the received dose-intensity before HDT was too low when compared with ACVBP and HDT and was given too early.
Mitochondrial Bax translocation partially mediates synergistic cytotoxicity between histone deacetylase inhibitors and proteasome inhibitors in glioma cells
Authors: Chunrong Yu, Bret B. Friday, Lin Yang, Peter Atadja, Dennis Wigle, Jann Sarkaria, Alex A. Adjei
Journal: Neuro-Oncology (2008)

The effects of combining histone deacetylase (HDAC) inhibitors and proteasome inhibitors were evaluated in both established glioblastoma multiforme (GBM) cell lines and short-term cultures derived from the Mayo Clinic xenograft GBM panel. Coexposure of LBH589 and bortezomib at minimally toxic doses of either drug alone resulted in a striking induction of apoptosis in established U251, U87, and D37 GBM cell lines, as well as in GBM8, GBM10, GBM12, GBM14, and GBM56 short-term cultured cell lines. Synergism of apoptosis induction was also observed in U251 cells when coexposing cells to other HDAC inhibitors, including LAQ824 and trichostatin A, with the proteasome inhibitor MG132, thus demonstrating a class effect. In U251 cells, bortezomib alone or in combination with LBH589 decreased Raf-1 levels and suppressed Akt and Erk activation. LBH589 or bortezomib alone increased expression of the cell cycle regulators p21 and p27. Additionally, the combination, but not the individual agents, markedly enhanced JNK activation. Synergistic induction of apoptosis after exposure to LBH589 and bortezomib was partially mediated by Bax translocation from the cytosol to the mitochondria resulting from Bax conformational changes. Bax translocation precedes cytochrome c release and apoptosis, and selective down-regulation of Bax using siRNA significantly mitigates the cytotoxicity of LBH589 and bortezomib. This combination regimen warrants further preclinical and possible clinical study for glioma patients.
The social origins of infantile colic: questionnaire study covering 76 747 infants
Authors: N S Crowcroft, D P Strachan
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To describe risk factors for infantile colic. <b>Design:</b> Questionnaire administered by health visitors. <b>Setting:</b> Sheffield. <b>Subjects:</b> Mothers of 76 747 infants born between 1 August 1975 and 31 May 1988, interviewed when the infant was 1 month old. <b>Main outcome measures:</b> Reporting of infantile colic and its duration; weight of infant, feeding, state of the home, socioeconomic characteristics of the parents, parents9 age, and mother9s parity. <b>Results:</b> The odds of reporting infantile colic were increased with breast feeding (odds ratio of breast <i>v</i> bottle feeding 1.35 (95% confidence interval 1.28 to 1.43), increasing parental age, lower parity, increasing parental age at leaving full time education, and more affluent homes and districts of residence. In a logistic regression analysis, mother9s age and parity and socioeconomic factors remained the most important risk factors for the reporting of infantile colic (each P &lt; 0.005), and the effect of breast feeding was attenuated (odds ratio of breast <i>v</i> bottle feeding 1.09 (1.02 to 1.15). <b>Conclusion:</b> At a population level, dietary factors contribute little to mothers9 reporting of infantile colic, and dietary change should not be the primary intervention. <h3>Key messages</h3> Infantile colic is poorly defined but commonly reported and causes parents appreciable distress Often the first advice that parents receive is to change the infant9s diet Slightly higher rates of reporting of infantile colic are found when infants are breast fed than bottle fed, so formulas based on cows9 and hence allergy to cows9 milk protein are unlikely to be important causes of infantile colic Social factors are most important, with older primigravid mothers who have a non-manual occupation and who stayed in full time education longest reporting the highest rates of colic in their infants Dietary change should not be the first intervention for colicky babies
Survival and safety of exemestane versus tamoxifen after 2–3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial
Authors: RC Coombes, LS Kilburn, CF Snowdon, R Paridaens, RE Coleman, SE Jones, J Jassem, CJH Van de Velde, T Delozier, I Alvarez, L Del Mastro, O Ortmann, K Diedrich, AS Coates, E Bajetta, SB Holmberg, D Dodwell, E Mickiewicz, J Andersen, PE Lønning, G Cocconi, J Forbes, M Castiglione, N Stuart, A Stewart, LJ Fallowfield, G Bertelli, E Hall, RG Bogle, M Carpentieri, E Colajori, M Subar, E Ireland, JM Bliss
Journal: The Lancet (2007)
Spirometry measurements in the morbid obesity
Authors: Khalil Abu Shams, Maria Hernandez, Amaia Iridoy, Susana Clemos
Journal: European Respiratory Journal (2012)

Background: The obesity is a particular case of thoracic respiratory function restriction. Obstructive Apnea Syndrome and hypoventilation have been described in relationship to the morbid obesity (MO).  Objective: To evaluate the alterations presented in spirometric measurements concerning the healthy subject with morbid obesity.  Methods: Spirometry and flow-volume curve were performed in 44 patients suffering of MO studied in our Departament. Of 44 cases, 8 were male (18.2%) with a mean age of 37+/- 8.8 years and 36 women (81.8%) with a mean age of 39.9 +/- 11.1 years.  Conclusions: There are no spirometry alterations in patients with morbid obesity with no history of cardiovascular, skeletal, neuromuscular or respiratory diseases.There are no difference between sexes.
Alterations in scalp blood flow after the epicutaneous application of 3% minoxidil and 0.1% hexyl nicotinate in alopecia
Authors: C.B. Bunker, PAULINE M. Dowd
Journal: British Journal of Dermatology (1987)

Journal Article Alterations in scalp blood flow after the epicutaneous application of 3% minoxidil and 0.1% hexyl nicotinate in alopecia Get access C.B. Bunker, C.B. Bunker Departments of Dermatology, The Middlesex Hospital and University College Hospital, London WI, U.K. Search for other works by this author on: Oxford Academic Google Scholar PAULINE M. Dowd PAULINE M. Dowd Departments of Dermatology, The Middlesex Hospital and University College Hospital, London WI, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 5, 1 November 1987, Pages 668–669, https://doi.org/10.1111/j.1365-2133.1987.tb07505.x Published: 01 November 1987
The Growth Hormone and Insulin-Like Growth Factor Axis
Authors: VINCENT ROELFSEMA, ROSS G. CLARK
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Renal failure is associated with dramatic changes in the growth hormone/insulin-like growth factor (GH/IGF) axis. In children, this results in growth retardation, which is treated with injections of recombinant human GH (rhGH). Given the many recent advances in the knowledge of the components of the GH/IGF axis, it is timely to review the role of GH in renal failure and to discuss likely new treatments for growth failure. Renal failure is not a state of GH deficiency but a state of GH and IGF resistance, making other approaches to manipulating the GH axis more logical than treatment with rhGH alone. Although in children rhGH is safe, in critically ill adults it can be lethal. As the mechanisms of these lethal actions of rhGH are unknown, caution is advised when using rhGH outside approved indications. In renal failure, an optimal balance between safety and efficacy for growth may be achieved with the use of the combination of rhGH and rhIGF-I, as animal studies have shown synergistic growth responses. However, inhibition of the GH axis, with the use of GH antagonists, is likely to be tested clinically given the beneficial effects of GH antagonists on renal function in animal models of renal disease. Manipulating IGF-I by either administering rhIGF-1 or its binding proteins or increasing IGF-I bioavailability with the use of IGF displacers could prove to be a safer and more effective alternative to the use of rhGH in renal failure. In the future, both rhGH and rhIGF-1 likely will be included in growth-promoting hormone cocktails tailored to correct specific growth disorders.
Inhibition of T cell activation and autoimmune diabetes using a B cell surface-linked CTLA-4 agonist
Authors: B. T. Fife
Journal: Journal of Clinical Investigation (2006)

CTL-associated antigen 4 (CTLA-4) engagement negatively regulates T cell activation and function and promotes immune tolerance. However, it has been difficult to explore the biology of selective engagement of CTLA-4 in vivo because CTLA-4 shares its ligands, B7-1 and B7-2, with CD28. To address this issue, we developed a Tg mouse expressing a single-chain, membrane-bound anti–CTLA-4 Ab (scFv) on B cells. B and T cells developed normally and exhibited normal phenotype in the steady state and after activation in these mice. However, B cells from scFv Tg+ mice (scαCTLA4+) prevented T cell proliferation and cytokine production in mixed lymphocyte reactions. Additionally, mice treated with scαCTLA4+ B cells had decreased T cell–dependent B cell Ab production and class switching in vivo after antigen challenge. Furthermore, expression of this CTLA-4 agonist protected NOD mice from spontaneous autoimmune diabetes. Finally, this disease prevention occurred in Treg-deficient NOD.B7-1/B7-2 double-knockout mice, suggesting that the effect of the CTLA-4 agonist directly attenuates autoreactive T cell activation, not Treg activation. Together, results from this study demonstrate that selective ligation of CTLA-4 attenuates in vivo T cell responses, prevents development of autoimmunity, and represents a novel immunotherapeutic approach for the induction and maintenance of peripheral tolerance.
Biphasic Patterns of Peripheral Insulin and Glucose Levels After Lunch in Normal Subjects
Authors: David C Robbins, Jonathan Jaspan, Barbara Vasquez, Eve Van Cauter
Journal: Diabetes Care (1987)

The dynamic relationship of glucose concentrations and insulin secretion during the postabsorptive state is complex and has been associated with a variety of cyclic rhythms. To study the pattern of insulin and glucose response immediately after a mixed meal, we collected blood every 15 min from 0730 to 1645 h from eight normal resting men (age 24.9 ± 2 . 1 yr). They took identically constituted mixed meals at 0800 and 1145 h. Concentrations of glucose and insulin were measured in samples taken throughout the study, whereas levels of C-peptide, glucagon, and a-NH2 were determined in samples taken after 1130 h only. Computer-assisted analysis was used to identify significant increments and declines in concentrations and to quantify the coincidence of peaks of glucose, C-peptide, glucagon, and α-NH2 with peaks of insulin. Coefficients of correlation between data points were calculated for each individual. The patterns of blood insulin and glucose after breakfast and lunch were different. After breakfast, a single simultaneous peak in insulin and glucose occurred ∼60 min after starting the meal. In contrast, the pattern after lunch in seven of the eight subjects was clearly biphasic. There were secondary, significant coincident peaks in serum insulin, glucose, and C-peptide occurring 1.75—2.25 h after the meal was served. The secondary peak appeared unrelated to the late absorption of protein because it was not associated with consistent changes in serum a-NH2 concentration. Erratic variations characterized the postlunch pattern of glucagon levels, excluding a role for this counterregulatory hormone in the control of the biphasic insulin and glucose response. Of the measured substances, only glucose, insulin, and C-peptide demonstrated significant cross-correlations. These data indicate that in this well-defined group of healthy volunteers, the response of plasma glucose, serum insulin, and C-peptide to lunch is biphasic.