tbuckley/cabot-search huggingface dataset:
Non-invasive cardiac output assessment in pulmonary hypertension
Authors: Laura Mayer, Friedrich Blumberg, Roland Wensel, Michael Pfeifer, Michael Arzt, Tobias Lange
Journal: European Respiratory Journal (2014)

Background : In patients with pulmonary hypertension (PH) invasive assessment of cardiac output (CO) is critical for diagnosis and evaluation of prognosis. Non-invasive measurement of CO would be invaluable in monitoring of disease progression and therapeutic response.   Aim:  To compare CO measured by thermodilution (TD) with pulmonary blood flow (as CO equivalent) determined by an inert gas rebreathing (RB) device using nitrous oxide (Innocor™, Innovision Denmark) at rest and on exercise.   Methods : In patients with suspected or confirmed PH, CO was assessed by TD and by RB with the Innocor™ system. Measurements were performed at rest (n=48) and during constant workrate exercise (n=23). Results were compared by means of correlation and Bland-Altman analysis.   Results : According to the Nice Classification, 20 patients were in group 1, 5 in group 2, 8 in group 3, 4 in group 4, and in 11 patients PH was excluded. CO TD  and CO RB  were closely correlated (Pearson coefficient 0.81, p TD  and CO RB  was 0.73 ± 0.98 L/min. at rest (p   Conclusion : In patients with suspected PH, non-invasive CO determination by RB is feasible and similarly accurate compared to TD at rest and on exercise. CO measured by RB is slightly lower than measured by TD, which has to be considered in the interpretation of test results.
Shp2 Negatively Regulates Growth in Cardiomyocytes by Controlling Focal Adhesion Kinase/Src and mTOR Pathways
Authors: Talita M. Marin, Carolina F.M.Z. Clemente, Aline M. Santos, Paty K. Picardi, Vinícius D.B. Pascoal, Iscia Lopes-Cendes, Mário J.A. Saad, Kleber G. Franchini
Journal: Circulation Research (2008)

The aim of this study was to investigate whether Shp2 (Src homology region 2, phosphatase 2) controls focal adhesion kinase (FAK) activity and its trophic actions in cardiomyocytes. We show that low phosphorylation levels of FAK in nonstretched neonatal rat ventricular myocytes (NRVMs) coincided with a relatively high basal association of FAK with Shp2 and Shp2 phosphatase activity. Cyclic stretch (15% above initial length) enhanced FAK phosphorylation at Tyr397 and reduced FAK/Shp2 association and phosphatase activity in anti-Shp2 precipitates. Recombinant Shp2 C-terminal protein tyrosine phosphatase domain (Shp2-PTP) interacted with nonphosphorylated recombinant FAK and dephosphorylated FAK immunoprecipitated from NRVMs. Depletion of Shp2 by specific small interfering RNA increased the phosphorylation of FAK Tyr397, Src Tyr418, AKT Ser473, TSC2 Thr1462, and S6 kinase Thr389 and induced hypertrophy of nonstretched NRVMs. Inhibition of FAK/Src activity by PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine} abolished the phosphorylation of AKT, TSC2, and S6 kinase, as well as the hypertrophy of NRVMs induced by Shp2 depletion. Inhibition of mTOR (mammalian target of rapamycin) with rapamycin blunted the hypertrophy in NRVMs depleted of Shp2. NRVMs treated with PP2 or depleted of FAK by specific small interfering RNA were defective in FAK, Src, extracellular signal-regulated kinase, AKT, TSC2, and S6 kinase phosphorylation, as well as in the hypertrophic response to prolonged stretch. The stretch-induced hypertrophy of NRVMs was also prevented by rapamycin. These findings demonstrate that basal Shp2 tyrosine phosphatase activity controls the size of cardiomyocytes by downregulating a pathway that involves FAK/Src and mTOR signaling pathways.
406-4 Mice lacking the transcription factor CHF1/Hey2 show decreased arterial neointimal formation after injury and impaired vascular smooth muscle cell responsiveness to growth factors
Authors: Yasuhiko Sakata, Fan Xiang, Zhiping Chen, Yoriko Kiriyama, Caramai N Kamei, Daniel I Simon, Michael T Chin
Journal: Journal of the American College of Cardiology (2004)
Human Renal Organic Anion Transporter 4 Operates as an Asymmetric Urate Transporter
Authors: Yohannes Hagos, Daniel Stein, Bernhard Ugele, Gerhard Burckhardt, Andrew Bahn
Journal: Journal of the American Society of Nephrology (2007)

Human organic anion transporter 4 (hOAT4) is located at the apical membrane of proximal tubule cells and involved in renal secretion and reabsorption of endogenous substances as well as many drugs and xenobiotics. This study reevaluated the physiologic role, transport mode, and driving forces of hOAT4. 6-Carboxyfluorescein (6-CF) uptake into HEK293 cells that stably expressed hOAT4 was saturable, resulting in a K(m) of 108 muM. 6-CF as well as [(3)H]estrone sulfate ([(3)H]ES) accumulation by HEK293-hOAT4 cells were abolished by ES, dehydroepiandrosterone sulfate, sulfinpyrazone, benzbromarone, and probenecid, whereas several OA, including p-aminohippurate (PAH), lactate, pyrazinoate, nicotinate, glutarate, and the diuretic hydrochlorothiazide (HCTZ) exhibited a slight or a NS inhibitory effect. PAH and glutarate are not taken up by HEK293-hOAT4 cells, but they trans-stimulated 6-CF and [(3)H]ES uptake, indicating an asymmetric interaction of hOAT4 with these substrates. In chloride-free medium, HEK293-hOAT4-mediated [(3)H]PAH efflux was almost abolished, whereas addition of ES restored it comparable to Ringer solution, consistent with a physiologic ES/PAH or PAH/Cl(-) exchange mode of hOAT4. Moreover, an acidification of the uptake medium increased 6-CF as well as [(3)H]ES uptake, which was reduced by nigericin, suggesting that hOAT4 also can operate as an OA/OH(-) exchanger. hOAT4 facilitates substantial uptake of [(14)C]urate, which was elevated 2.6-fold by intracellular HCTZ. Thus, hOAT4 is the long-postulated, low-affinity apical urate anion exchanger that facilitates HCTZ-associated hyperuricemia.
Seasonality and attendance at a pulmonary rehabilitation programme
Authors: G. E. Walker, C. Lee, S. L. Elkin
Journal: Thorax (2010)

Pulmonary rehabilitation (PR) programmes have been shown to reduce symptoms, improve exercise tolerance and reduce readmission rates in chronic obstructive pulmonary disease (COPD).1 2 PR has the potential to reduce the economic burden of COPD upon the NHS but, if poor attendance results in groups running at less than capacity, the cost-effectiveness of the service is markedly reduced. Understanding and responding to the factors that influence attendance is vital to ensuring maximum benefit is gained from PR programmes. The role of seasonality in attendance at PR programmes has not previously been evaluated, and there is …
Bone Marrow Microenvironmental Changes Underlie Reduced RAG-mediated Recombination and B Cell Generation in Aged Mice
Authors: Joseph E. Labrie, Alex P. Sah, David M. Allman, Michael P. Cancro, Rachel M. Gerstein
Journal: The Journal of Experimental Medicine (2004)

During aging, adaptive immunity is severely compromised, due in part to decreased production of B lymphocytes and loss of immunoglobulin (Ig) diversity. However, the molecular mechanisms that underlie age-associated diminished B cell production remain unclear. Using in vivo labeling, we find that this reduction in marrow pre–B cells reflects increased attrition during passage from the pro–B to pre–B cell pool. Analyses of reciprocal bone marrow chimeras reveal that the magnitude and production rates of pre–B cells are controlled primarily by microenvironmental factors, rather than intrinsic events. To understand changes in pro–B cells that could diminish production of pre–B cells, we evaluated rag2 expression and V(D)J recombinase activity in pro–B cells at the single cell level. The percentage of pro–B cells that express rag2 is reduced in aged mice and is correlated with both a loss of V(D)J recombinase activity in pro–B cells and reduced numbers of pre–B cells. Reciprocal bone marrow chimeras revealed that the aged microenvironment also determines rag2 expression and recombinase activity in pro–B cells. Together, these observations suggest that extrinsic factors in the bone marrow that decline with age are largely responsible for less efficient V(D)J recombination in pro–B cells and diminished progression to the pre–B cell stage.
Double-Blind, Randomized Study Evaluating the Glycemic and Anti-inflammatory Effects of Subcutaneous LY2189102, a Neutralizing IL-1β Antibody, in Patients With Type 2 Diabetes
Authors: Joanne Sloan-Lancaster, Eyas Abu-Raddad, John Polzer, Jeffrey W. Miller, Joel C. Scherer, Andrea De Gaetano, Jolene K. Berg, William H. Landschulz
Journal: Diabetes Care (2013)

Inflammation is associated with pancreatic β-cell apoptosis and reduced insulin sensitivity. Literature suggests that interleukin (IL)-1β may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). This study aimed to determine the efficacy, safety, and tolerability of LY2189102, a neutralizing IL-1β antibody, in T2DM patients.Phase II, randomized, double-blind, parallel, placebo-controlled study of subcutaneous LY2189102 (0.6, 18, and 180 mg) administered weekly for 12 weeks in T2DM patients on diet and exercise, with or without approved antidiabetic medications.LY2189102 reduced HbA1c at 12 weeks (adjusted mean differences versus placebo: -0.27, -0.38 and -0.25% for 0.6, 18 and 180 mg doses, respectively), and fasting glucose at multiple time points compared with placebo. LY2189102 also reduced postprandial glycemia, and inflammatory biomarkers, including hs-CRP and IL-6. LY2189102 was generally well tolerated.Weekly subcutaneous LY2189102 for 12 weeks was well tolerated, modestly reduced HbA1c and fasting glucose, and demonstrated significant anti-inflammatory effects in T2DM patients. Neutralizing IL-1β holds promise as a convenient adjuvant treatment for T2DM.
Towards improving cardiovascular risk management in patients with rheumatoid arthritis: the need for accurate risk assessment
Authors: C. S. Crowson, S. E. Gabriel
Journal: Annals of the Rheumatic Diseases (2011)

Numerous reports of the increased incidence of cardiovascular disease (CVD) among patients with rheumatoid arthritis (RA) have been published during the past decade.1 2 In addition, the increased risk of CVD in patients with RA cannot be explained by traditional CV risk factors alone.3 4 While these reports have increased awareness of CV morbidity and mortality among patients with RA, the lack of CV risk assessment tools and evidence-based practice guidelines developed specifically for patients with RA has slowed the translation of this knowledge into clinical decision making. The following two case studies illustrate the need for accurate RA-specific CV risk assessment tools.

The first patient, a woman, was diagnosed as having RA at age 40 with rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity and rheumatoid nodules present at diagnosis. She was a non-smoker and non-diabetic with total cholesterol of 6.7 mmol/litre (258 mg/dl), high-density lipoprotein cholesterol (HDL-c) of 1.4 mmol/litre (54 mg/dl) and a systolic blood pressure of 120 mm Hg. The SCORE (for 'Systematic COronary Risk Evaluation') risk assessment for populations at high CVD risk categorised her 10-year risk of fatal CVD as <1% and the general Framingham Risk Score (FRS) estimated her 10-year risk for any CVD event as 4%.5 6 Despite these low risk assessments, she experienced a myocardial infarction (MI) at age 45. Thus, the SCORE and FRS did not accurately predict CV risk for this patient.

The second patient, a man, was diagnosed as having RA at age 46 with RF/ACPA positivity and rheumatoid vasculitis present at diagnosis. He was a non-smoker and non-diabetic with total cholesterol of 8.8 mmol/litre (341 mg/dl), HDL-c of 2.0 mmol/litre (76 mg/dl), a systolic blood pressure of 140 mm Hg and normal body mass index (26 kg/m2). His SCORE risk was 2.6% …
Correlation of Cell Kinetic Findings With Morphology of Non-Hodgkin's Malignant Lymphomas 2
Authors: Rosella Silvestrini, Rita Piazza, Alberto Riccardi, Franco Rilke
Journal: JNCI Journal of the National Cancer Institute (1977)

Kinetic studies were carried out on 6 benign and 37 malignant lymph nodes from patients with non-Hodgkin's malignant lymphomas (ML). The labeling index, DNA content, and cell distribution through the cell cycle were analyzed in the ML, which were classified according to the Kiel classification. Approximately 90% of the ML studied showed a clear diploidy; the only cases of polyploidy were limited to some centroblastic-centrocytic ML with more than 30% malignant centroblasts and to be single centroblastic ML. The labeling indexes ranged from 0.05 to 33%. No correlation was found between the proliferative rate and the degree of ploidy, while a grading of labeling index was found in relation to the three main DNA distribution patterns observed (i.e., G1 peak, S accumulation, and bimodal distribution through the cell cycle). From a kinetic point of view, the most heterogeneous groups were the lymphoplasmacytoid (subtype polymorphous) and centroblastic-centrocytic ML, where the degree of proliferation increased as the mixture of cell type (relative to the former group) and the malignant centroblastic component (relative to the latter group) increased.
Cladribine with Immediate Rituximab for the Treatment of Patients with Variant Hairy Cell Leukemia
Authors: Robert J. Kreitman, Wyndham Wilson, Katherine R. Calvo, Evgeny Arons, Laura Roth, Jeffrey Sapolsky, Hong Zhou, Mark Raffeld, Maryalice Stetler-Stevenson
Journal: Clinical Cancer Research (2013)

Abstract Purpose: In contrast with the classic form, variant hairy cell leukemia (HCLv) responds poorly to single-agent purine analogs, expresses unmutated BRAF, has shorter overall survival, and lacks effective standard therapy. No treatment has achieved a high complete remission (CR) rate even in small series, and of 39 reported cases from six studies, overall response rate after cladribine was 44% with 8% CRs. Rituximab has been found to increase the sensitivity of malignant cells to cladribine, suggesting that combination with cladribine might improve response in HCLv. To test this hypothesis, patients with HCLv were treated with simultaneous cladribine and rituximab. Experimental Design: Patients with HCLv with 0 to 1 prior courses of cladribine received cladribine 0.15 mg/kg for days 1 to 5, with eight weekly doses of rituximab 375 mg/m2 beginning day 1. Restaging was performed, and minimal residual disease (MRD) in blood and marrow was quantified using PCR, immunohistochemistry, and flow cytometry. Results: By 6 months, 9 (90%) of 10 patients achieved CR, compared with 3 (8%) of 39 reported cases treated with cladribine alone (P &amp;lt; 0.0001). Of the 9 CRs, 8 remain free of MRD at 12 to 48 (median 27) months of follow-up. No dose-limiting toxicities were observed when beginning cladribine and rituximab on the same day, although most patients required short-term steroids to prevent and treat rituximab infusion reactions. Cytopenias in CRs resolved in 7 to 211 (median 34) days without major infections. Conclusion: Although cladribine alone lacks effectiveness for early or relapsed HCLv, cladribine with immediate rituximab achieves CRs without MRD and is feasible to administer. Clin Cancer Res; 19(24); 6873–81. ©2013 AACR.
Do Rectal Cancer Patients with <i>PIK3CA</i> Mutations Benefit from Preoperative Radiotherapy with Regard to Local Recurrences?
Authors: Youji He, Laura J. Van't Veer, Marta Lopez-Yurda, Cornelis J.H. van de Velde, Corrie A.M. Marijnen
Journal: Clinical Cancer Research (2010)

Preoperative radiation (PRT) significantly reduces local recurrences (LR) in rectal cancer. Identifying patients at risk for LR allows for refinement in patient selection for PRT. We previously demonstrated a PIK3CA mutation prevalence of 7.9% in rectal cancer and a strong association with increased
Provoking dose of mannitol to assess airway hyperresponsiveness in asthma: A retrospective analysis
Authors: S.D. Anderson, J.D. Brannan, H. Koskela, R. Freed-Martens, J.D. Leuppi, K. Holzer, B. Lipworth, G.P. Currie, M. Sue-Chu, C.P. Perry
Journal: Journal of Allergy and Clinical Immunology (2005)
DERMATOLOGICAL JOURNALS IN BRITAIN
Authors: ARTHUR ROOK
Journal: British Journal of Dermatology (1970)

Journal Article DERMATOLOGICAL JOURNALS IN BRITAIN ARTHUR ROOK Get access ARTHUR ROOK ARTHUR ROOK Department of Dermatology, Addenbrooke's Hospital, Cambridge Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 83, Issue 1, 1 July 1970, Pages 109–118, https://doi.org/10.1111/j.1365-2133.1970.tb15033.x Published: 01 July 1970
Control of mating preferences in mice by genes in the major histocompatibility complex.
Authors: K Yamazaki, E A Boyse, V Miké, H T Thaler, B J Mathieson, J Abbott, J Boyse, Z A Zayas, L Thomas
Journal: The Journal of Experimental Medicine (1976)

When a male mouse is presented with two H-2 congenic two female in estrus, his choice of a mate is influenced by their H-2 types. The term "strain preference" is used to describe the general tendency of the male population of one inbred strain to prefer two female of one H-2 type rather than another. The term "consistency of choice" is used to describe the added tendency of particular two males of one inbred strain, in sequential mating trials, to prefer two females of the H-2 type they chose in previous trials. Statistical analysis showed trends in the data that support the following conclusions: (a) The choice is made by the male, not the female. (b) The strain preference of two males may favor two females of dissimilar H-2 type (four of six comparisons), or of similar H-2 type (one of six comparisons). (c) Consistency of choice does not always correspond with strain preference. In one of six comparisons of H-2 genotypes there was no strain preference but pronounced consistency of choice by individual two male.This suggests memory, but fortuitous bias is not excluded. (d) Strain preference of the same male population may favor two male of the same or a different H-2 type, depending on which different H-2 type is offered as the choice alternative to self.These findings conform to a provisional model in which olfactory mating preference is governed by two linked genes in the region of H-2, one for the female signal and one for the male receptor. These mating preferences could in natural populations serve the purpose of increasing the representation of particular H-2 haplotypes or of maintaining heterozygosity of genes in the region of H-2.
Leukostasis associated with blood transfusion in acute myeloid leukaemia.
Authors: A L Harris
Journal: BMJ (1978)

Three patients with acute myeloblastic leukaemia and blast cell counts greater than 100 X 10(9)/1 (100 000/mm3) died unexpectedly soon after blood transfusion. In two cases postmortem examination disclosed cerebral leukostasis. Analysis of the records from the MRC9s fourth and fifth acute myeloid leukaemia trials showed that in the first week after diagnosis mortality was five times greater in patients with blast counts above 100 X 10(9)/1 than in patients with lower counts. Age and platelet count did not explain this excess. The mean haemoglobin concentration in the patients with high blast counts who died within the first week was 10.5 +/- 2.8 g/dl, which was significantly higher than that in the surviving group (7.6 +/- 2.4 g/dl). Only half the patients received chemotherapy within two days of diagnosis. Leukostasis is an important cause of early death in patients with high blast counts, and the increase in viscosity produced by transfusing to a haemoglobin concentration above 10 g/dl may lead to sudden deterioration. Transfusion to such concentrations should be avoided until the blast count has been reduced by early chemotherapy.
Glottic aperture and effective minute ventilation during nasal two-level positive pressure ventilation in spontaneous mode.
Authors: V F Parreira, P Delguste, V Jounieaux, G Aubert, M Dury, D O Rodenstein
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Our goal was to verify glottic behavior and its effects on effective minute ventilation during intermittent positive pressure ventilation applied at increasing inspiratory pressure levels through a nasal mask (nIPPV) using a two-level positive pressure ventilator (two-level IPPV) in spontaneous mode. Ten subjects were studied while awake. The spontaneous mode was used at three levels of inspiratory positive airway pressure (IPAP): 10, 15, and 20 cm H2O. The expiratory pressure was kept at 4 cm H2O. Records of spontaneous breathing without nIPPV were also performed. The glottis was continuously monitored through a fiberoptic bronchoscope. We measured, breath by breath, the widest inspiratory angle formed by the vocal cords at the anterior commissure, the corresponding tidal volume (with respiratory inductive plethysmography), the respiratory frequency and other indices. Our data during wakefulness show that inspiratory pressures of 10 and 15 cm H2O did not result in increases in effective minute ventilation with respect to spontaneous breathing. Only at 20 cm H2O of IPAP did effective minute ventilation increase. This was due essentially to a decrease in respiratory frequency with increasing pressures, offsetting increases in tidal volume at 10 and 15, but not at 20 cm H2O of inspiratory pressure. Changes in end-tidal CO2 suggest that alveolar ventilation increased due to the change in breathing pattern. Contrary to what we observed previously with either two-level IPPV used in the controlled mode, or nIPPV performed with volumetric ventilators, the glottis did not play any noticeable role in the control of effective minute ventilation.
Genetically Engineered Insulin Analogs: Diabetes in the New Millenium
Authors: Zoltan Vajo, William C. Duckworth
Journal: Pharmacological Reviews (2000)

Tight glucose control is essential to minimize complications in diabetic patients. However, the pharmacokinetic characteristics of the currently available rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. Until recently, improvements in insulin formulations were seriously limited as advances were only achieved in insulin purity, species, and characteristics of the retarding agent. The availability of molecular genetic techniques opened new windows to create insulin analogs by changing the structure of the native protein and to improve the therapeutic properties. The first clinically available insulin analog, Lispro, confirmed the hopes by showing that improved glycemic control can be achieved without an increase in hypoglycemic events. This requires, however, optimal basal insulin replacement, either by multiple daily injections of neutral protein Hagedorn (NPH) insulin or by insulin pump. Evidence suggests that short-acting insulin analogs would be better matched by a true basal insulin than by the erratically absorbed and rather short-acting NPH insulin. Therefore, future availability of long-acting analogs raises the hope to realize the true potential benefits of the currently available short-acting analog, Lispro, and of those still awaiting approval. The introduction of new short-acting and the first truly long-acting analogs, the development of analogs with increased stability, less variability and perhaps selective action will help to develop more individualized treatment strategies targeted to specific patient characteristics and to achieve further improvements in glycemic control.