tbuckley/cabot-search huggingface dataset:
Phase I Trial of Pelvic Radiation, Weekly Cisplatin, and 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP, NSC #663249) for Locally Advanced Cervical Cancer
Authors: Charles A. Kunos, Steven Waggoner, Vivian von Gruenigen, Elisa Eldermire, John Pink, Afshin Dowlati, Timothy J. Kinsella
Journal: Clinical Cancer Research (2010)

This study assessed the safety/tolerability, pharmacokinetics, and clinical activity of three times weekly i.v. 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in combination with once-weekly i.v. cisplatin and daily pelvic radiation in patients with gynecologic malignancies. 3-AP is a novel small-molecule inhibitor of ribonucleotide reductase (RNR) and is being tested as a potential radiosensitizer and chemosensitizer.Patients with stage IB2 to IVB cervical cancer (n = 10) or recurrent uterine sarcoma (n = 1) were assigned to dose-finding cohorts of 2-hour 3-AP infusions during 5 weeks of cisplatin chemoradiation. Pharmacokinetic and methemoglobin samples and tumor biopsy for RNR activity were obtained on day 1 and day 10. Clinical response was assessed.The maximum tolerated 3-AP dose was 25 mg/m(2) given three times weekly during cisplatin and pelvic radiation. Two patients experienced manageable 3-AP-related grade 3 or 4 electrolyte abnormalities. 3-AP pharmacokinetics showed a 2-hour half-life, with median peak plasma concentrations of 277 ng/mL (25 mg/m(2)) and 467 ng/mL (50 mg/m(2)). Median methemoglobin levels peaked at 1% (25 mg/m(2)) and 6% (50 mg/m(2)) at 4 hours after initiating 3-AP infusions. No change in RNR activity was found on day 1 versus day 10 in six early complete responders, whereas elevated RNR activity was seen on day 10 as compared with day 1 in four late complete responders (P = 0.02). Ten (100%) patients with stage IB2 to IVB cervical cancer achieved complete clinical response and remained without disease relapse with a median 18 months of follow-up (6-32 months).3-AP was well tolerated at a three times weekly i.v. 25 mg/m(2) dose during cisplatin and pelvic radiation. Clin Cancer Res; 16(4); 1298-306.
<i>Bim</i> Polymorphisms: Influence on Function and Response to Treatment in Children with Acute Lymphoblastic Leukemia
Authors: Vincent Gagné, Julie Rousseau, Malgorzata Labuda, Bahram Sharif-Askari, Ivan Brukner, Caroline Laverdière, Francesco Ceppi, Stephen E. Sallan, Lewis B. Silverman, Donna Neuberg, Jeffery L. Kutok, Daniel Sinnett, Maja Krajinovic
Journal: Clinical Cancer Research (2013)

Corticosteroids induce apoptosis in the malignant lymphoid cells and are critical component of combination therapy for acute lymphoblastic leukemia (ALL). Several genome-wide microarray studies showed major implication of proapoptotic Bim in mediating corticosteroid-related resistance in leukemia cells.We investigated Bim gene polymorphisms and their association with childhood ALL outcome, and the mechanism underlying the observed finding.Lower overall survival (OS) was associated with Bim C29201T located in Bcl-2 homology 3 (BH3) domain (P = 0.01). An association remained significant in multivariate model (P = 0.007), was more apparent in high-risk patients (P = 0.004) and patients treated with dexamethasone (P = 0.009), and was subsequently confirmed in the replication patient cohort (P = 0.03). RNA analysis revealed that C29201T affects generation of γ isoforms (γ1) that lack proapoptotic BH3 domain. The phenotypic effect was minor suggesting the influence of additional factors that may act in conjunction with Bim genotype. Combined analysis with Mcl gene polymorphism (G-486T) revealed profound reduction in OS in individuals with both risk genotypes (P < 0.0005 in discovery and P = 0.002 in replication cohort) and particularly in high-risk patients (P ≤ 0.008).Increased expression of prosurvival Mcl1 and presence of Bim isoforms lacking proapoptotic function might explain marked reduction of OS in a disease and dose-dependent manner in ALL patients carrying Bim- and Mcl1-risk genotypes.
Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro.
Authors: R Wilson, T Pitt, G Taylor, D Watson, J MacDermot, D Sykes, D Roberts, P Cole
Journal: Journal of Clinical Investigation (1987)

Pseudomonas aeruginosa culture filtrates varied in their ability to slow human ciliary beat frequency (7-71%). This activity did not correlate with known virulence factors. However, a close correlation (r = 0.97) existed between ciliary slowing and pigment content. In a prolonged culture, the increase in activity correlated (r = 0.94) with pigment accumulation. Gel filtration of lyophilized filtrate yielded a single peak of activity corresponding to the pigment fraction. Pyocyanin extracted from an active strain, and 1-hydroxyphenazine were purified by high performance liquid chromatography, and characterized by ultraviolet absorbance spectra and mass spectrometry. Both slowed cilia in a dose-dependent manner, and were synthesized and shown to be indistinguishable from the biological compounds. Pyocyanin caused gradual onset of slowing and ultimate widespread ciliostasis with epithelial disruption. 1-hydroxyphenazine caused rapid onset of ciliary slowing associated with dyskinesia and ciliostasis. Pyocyanin assayed within filtrates accounted for a significant proportion of the bioactivity present.
Effect of supplementary food on suckling patterns and ovarian activity during lactation
Authors: J S Forsyth
Journal: BMJ (1981)

Two of the three patients who had to stop medica- tion because of increased bone pain did have a serum phosphorus level which rose above 1 3 mmol/l (4 0 mg/dl).1''This effect of disodium etidronate on renal tubular reabsorption of phosphate may occur with dosages as low as 10 mg/kg/24 h1213 and in our experience even at lower dosages."''Hence one should reduce the dose if there is any increase in the serum phosphorus level.The question as to whether or not, or more specifically at what dosages, disodium etidronate increases bone pain or bone fracture has been the matter of much debate.It should be pointed out that this is a question which has arisen with the disodium etidronate era of therapy.If one only considers the "large" series (>30 patients) of pagetic patients treated with calcitonin and reported all over the world (be it in the United States,'4 in Australia,'516 in England,'7 or in France18), exacerbation of bone pain or incidence of fractures never had to be given any consideration.Preliminary data which we have obtained with a diphosphonate which does not produce a mineral- isation defect-that is, 3-amino-1-hydroxypropylidene-1,1-diphosphonate or APD, administered orally at a dosage of 600 mg daily, showed that the production of negative focal bone balances may be a feature unique to disodium etidronate.If Dr Hosking surprisingly overlooked all the roentgenologic data that we have provided on disodium etidronate toxicity, he at least pointed out that this and related compounds do hold great promise, provided that unex- pected side effects, not related to bone, do not appear in the long term.
SEARCHING FOR THE BIOLOGICAL PATHWAYS BETWEEN STRESS AND HEALTH
Authors: Shona Kelly, Clyde Hertzman, Mark Daniels
Journal: Annual Review of Public Health (1997)

Population-based, person-specific health surveys, with concomitant biological measures, should provide important information about the processes by which socioeconomic and psychosocial factors embed themselves in human health. Questionnaire responses allow for assessment of the perceived psychosocial environment, but biological measurements will measure the status of the psychoneuroimmunology/ psychoneuroendocrinology (PNI/PNE) pathways and may allow us to identify people who have "adapted" to their stress because of experience, expectations, stoicism, etc. This review sets criteria to evaluate potential physiological markers of chronic stress. Because population health surveys involve a massive number of samples, special consideration must be given to the laboratory analysis method and transportation time of the markers chosen. We reviewed five areas: glycosylated proteins, the immune system, hemostasis peripheral benzodiazepine receptors, and the waist-hip ratio.
Carotid intima-media thickness in Japanese type 2 diabetic subjects: predictors of progression and relationship with incident coronary heart disease.
Authors: Y Yamasaki, M Kodama, H Nishizawa, K Sakamoto, M Matsuhisa, Y Kajimoto, K Kosugi, Y Shimizu, R Kawamori, M Hori
Journal: Diabetes Care (2000)

To examine carotid intima-media thickness (IMT), predictors of its progression, and its relationship with incident coronary heart disease (CHD) in type 2 diabetic Japanese patients.Carotid IMT of 287 subjects with type 2 diabetes (mean age 61.6 years) without CHD or cerebrovascular disease was examined at baseline and after a mean follow-up of 3.1 years.The annual progression of IMT (means +/- SEM) was 0.04+/-0.004 mm/year. Stepwise multivariate analysis demonstrated that independent risk factors for progress of IMT were the initial IMT (P<0.001), the average HbA1c level (P<0.001), and age (P = 0.001). Both the initial IMT (odds ratio [OR] 4.9, 95% CI 1.7-14.1) and a low average HDL cholesterol (OR 0.2, 0.1-0.8) were identified as predictors of incident nonfatal CHD (angina pectoris or nonfatal myocardial infarction; 3-year incidence 10.1%) after adjusting for age, sex, average HbA1c, and other risk factors.The predictors of the progression of carotid IMT in Japanese type 2 diabetic subjects were its baseline thickness and the average HbA1c during the follow-up. Baseline carotid IMT and low HDL cholesterol predicted the incidence of nonfatal CHD.
Activation of the Heart by Donor Brain Death Accelerates Acute Rejection After Transplantation
Authors: Markus J. Wilhelm, Johann Pratschke, Francisca Beato, Maarten Taal, Mamoru Kusaka, Wayne W. Hancock, Nicholas L. Tilney
Journal: Circulation (2000)

Background —Donor brain death upregulates expression of inflammatory mediators in the heart. It is hypothesized that these nonspecific changes trigger and amplify acute rejection in unmodified recipients compared with hearts from normal living donors. We examined the inflammatory and immunological consequences of gradual-onset donor brain death on cardiac allografts after transplantation. Methods and Results —Functioning hearts were engrafted from normotensive donors after 6 hours of ventilatory support. Hearts from brain-dead rats (Fisher, F344) were rejected significantly earlier (mean±SD, 9.3±0.6 days) by their (Lewis) recipients than hearts from living donor controls (11.6±0.7 days, P =0.03). The inflammatory response of such organs was accelerated, with rapid expression of cytokines, chemokines, and adhesion molecules and brisk infiltration of associated leukocyte populations. Upregulation of major histocompatibility class II antigens increased organ immunogenicity. Acute rejection evolved in hearts from brain-dead donors more intensely and at a significantly faster rate than in controls. Conclusions —Donor brain death is deleterious to transplanted hearts. The resultant upregulation of inflammatory factors provokes host immune mechanisms and accelerates the acute rejection process in unmodified hosts.
Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles. A Cochrane review †
Authors: Madelon van Wely, Irene Kwan, Anna L. Burt, Jane Thomas, Andy Vail, Fulco Van der Veen, Hesham G. Al-Inany
Journal: Human Reproduction Update (2012)

Several systematic reviews compared recombinant gonadotrophin with urinary gonadotrophins (HMG, purified FSH and highly purified FSH) for ovarian hyperstimulation in IVF and ICSI cycles and these reported conflicting results. Each of these reviews used different inclusion and exclusion criteria for trials. Our aim in producing this review was to bring together all randomized studies in this field under common inclusion criteria with consistent and valid statistical methods.
Comparison of formoterol, salbutamol and salmeterol in methacholine-induced severe bronchoconstriction
Authors: M J Politiek, M Boorsma, R Aalbers
Journal: European Respiratory Journal (1999)

The onset of the bronchodilating effect of formoterol (12 microg by Turbuhaler) was compared with that of salbutamol (50 microg by Turbuhaler), salmeterol (50 microg by Diskhaler) and placebo in methacholine-induced severe bronchoconstriction. Seventeen subjects with mild-to-moderate asthma completed this randomized, double blind, cross-over, double-dummy study. On four study days, baseline forced expiratory volume in one second (FEV1) was recorded and the subjects were challenged with methacholine until FEV1 fell by at least 30%. Immediately thereafter, the study drugs were inhaled and lung function was assessed for 60 min. The geometric mean time for FEV1 to return to 85% of baseline was 7.2 min with formoterol, 6.5 min with salbutamol, 14.1 min with salmeterol and 34.7 min with placebo (p=0.0001, overall ANOVA). The difference between formoterol and salmeterol was statistically significant (p=0.01); there was no difference between formoterol and salbutamol (p=0.69). In conclusion, formoterol reversed methacholine-induced severe bronchoconstriction as rapidly as salbutamol and more rapidly than salmeterol. Classifying beta2-agonists as "fast"- and "slow"- acting may be supplemental to "short"- and "long"-acting.
Is the Number of Documented Diabetes Process-of-Care Indicators Associated With Cardiometabolic Risk Factor Levels, Patient Satisfaction, or Self-Rated Quality of Diabetes Care?
Authors: Ronald T. Ackermann, Theodore J. Thompson, Joseph V. Selby, Monika M. Safford, Mark Stevens, Arleen F. Brown, K.M. Venkat Narayan
Journal: Diabetes Care (2006)

Simple process-of-care indicators are commonly recommended to assess and compare quality of diabetes care across health plans. We sought to determine whether variation in the number of simple diabetes processes of care across provider groups is associated with variation in other quality indicators, including cardiometabolic risk factor levels, patient satisfaction with care, or patient-rated quality of care.We used cross-sectional survey and chart audit data for 8,733 patients with diabetes who received care from 68 provider groups nested in 10 health plans that participated in the Translating Research Into Action for Diabetes study. Analyses using hierarchical regression models assessed associations of the mean number of seven simple process measures with each of the following: HbA(1c) (A1C), systolic blood pressure (SBP), HDL and LDL cholesterol levels, patient satisfaction with care, and patient-rated quality of care.After adjusting for case-mix differences across groups and plans, an average of one additional documented process of care for each patient in a group or plan was associated with significantly lower mean LDL cholesterol levels (-4.51 mg/dl [95% CI 1.46-7.58]) but not with A1C, SBP, or HDL cholesterol levels. The number of care processes documented was associated with patient satisfaction measures and self-rated quality of diabetes care.Variation in the number of simple process-of-care indicators across provider groups or health plans is associated with differences in patient-centered measures of quality, but assessment of the quality of cardiometabolic risk factor control will require more advanced clinical performance indicators.
HNK-I antibody reacts with peripheral nerves and sweat glands in the skin
Authors: I. ANDO, K. TAMAKI
Journal: British Journal of Dermatology (1985)

Journal Article HNK‐I antibody reacts with peripheral nerves and sweat glands in the skin Get access I. ANDO, I. ANDO Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113, Japan Iwao Ando, M.D., Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113, Japan. Search for other works by this author on: Oxford Academic Google Scholar K. TAMAKI K. TAMAKI Department of Dermatology, Faculty of Medicine, University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue 2, 1 August 1985, Pages 175–178, https://doi.org/10.1111/j.1365-2133.1985.tb02061.x Published: 01 August 1985 Article history Accepted: 07 January 1985 Published: 01 August 1985
The role of phosphate in the secretion of parathyroid hormone in man
Authors: Eric Reiss, Janet M. Canterbury, Margaret A. Bercovitz, Edwin L. Kaplan
Journal: Journal of Clinical Investigation (1970)

In man, oral administration of 1 g of phosphorus resulted in a 60-125% increase in serum immunoassayable parathyroid hormone (PTH) concentration. Peak PTH levels were attained in 1 hr, and PTH returned to base line levels in 2 hr. This increase in PTH appeared to be initiated by a very small decrease of total and ionized calcium and was abolished by a calcium infusion. There was no correlation between serum phosphorus and PTH. The experiments show that oral phosphorus administration initiates a calcium-mediated control system for PTH secretion and that this system operates very sensitively in man.
A decade at the helm of Cardiovascular Research, the basic science flagship of the ESC
Authors: H. Michael Piper, D. Garcia-Dorado
Journal: Cardiovascular Research (2012)

With this editorial, the present editorial team of Cardiovascular Research ( Figure 1 ) will say farewell to all authors, reviewers, and readers of the journal and thank them all for their support. We will hand over the journal to the new editor-in-chief, Karin Sipido, and her new team by the end of 2012. We wish them success and the continuing support of the scientific community. 



Figure 1 
A moment soon to come: The old crew left ashore while the flagship journal sails out to the high seas under new command. Back row from left : H. Michael Piper, Editor-in-Chief; Elizabeth A. Martinson, Managing Editor; Associate Editors Javier Inserte, Antonia Sambola, Marisol Ruiz-Meana, Jose Antonio Barrabes, and Gerhild Euler; Editorial Assistant Judith Lehnhardt. Front row from left : Thomas Noll, Associate Editor; Giuliana Rios-Quinones, Editorial Assistant; Klaus-Dieter Schluter, Associate Editor; David Garcia-Dorado, Co-Editor. Not shown : Associate Editors Heinrich Sauer and Rainer Schulz; Editorial Assistants Anette Gralla and Jasmine Gaspar Dorr.



The present editorial team has served for a full decade, starting on 1 January 2003. We made ∼18 000 decisions on manuscript submissions and were supported by ∼40 000 sets of reviewer comments throughout these years. For the editors, it has been a very exciting and rewarding time, both in terms of their own scientific learning and the many interesting personal contacts they made.

We have taken it as an outstanding honour to be entrusted by the …
Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity
Authors: Xuyu Zhou, Lukas T. Jeker, Brian T. Fife, Shirley Zhu, Mark S. Anderson, Michael T. McManus, Jeffrey A. Bluestone
Journal: The Journal of Experimental Medicine (2008)

A new regulatory T (T reg) cell–specific, FoxP3-GFP-hCre bacterial artificial chromosome transgenic mouse was crossed to a conditional Dicer knockout (KO) mouse strain to analyze the role of microRNAs (miRNAs) in the development and function of T reg cells. Although thymic T reg cells developed normally in this setting, the cells showed evidence of altered differentiation and dysfunction in the periphery. Dicer-deficient T reg lineage cells failed to remain stable, as a subset of cells down-regulated the T reg cell–specific transcription factor FoxP3, whereas the majority expressed altered levels of multiple genes and proteins (including Neuropilin 1, glucocorticoid-induced tumor necrosis factor receptor, and cytotoxic T lymphocyte antigen 4) associated with the T reg cell fingerprint. In fact, a significant percentage of the T reg lineage cells took on a T helper cell memory phenotype including increased levels of CD127, interleukin 4, and interferon γ. Importantly, Dicer-deficient T reg cells lost suppression activity in vivo; the mice rapidly developed fatal systemic autoimmune disease resembling the FoxP3 KO phenotype. These results support a central role for miRNAs in maintaining the stability of differentiated T reg cell function in vivo and homeostasis of the adaptive immune system.
Cloning and characterization of allograft inflammatory factor-1: a novel macrophage factor identified in rat cardiac allografts with chronic rejection.
Authors: U Utans, R J Arceci, Y Yamashita, M E Russell
Journal: Journal of Clinical Investigation (1995)

The development of arteriosclerotic lesions in the Lewis to F344 rat model of chronic cardiac rejection is characterized by macrophage adhesion to the vessel lumen and macrophage infiltration in the neointima prior to smooth muscle cell accumulation. We report the cloning and characterization of allograft inflammatory factor-1 (AIF-1), a novel cDNA that is expressed early and persistently in chronically rejecting cardiac allografts but is absent in cardiac syngrafts and host hearts. The full-length cDNA codes for a hydrophilic polypeptide of 17 kD that contains a 12-amino acid region similar to an EF-hand (calcium-binding) domain. In cardiac allografts AIF-1 transcripts and protein localized to infiltrating mononuclear cells. Analysis of isolated cell populations confirmed that AIF-1 was selectively expressed in macrophages and neutrophils and demonstrated that AIF-1 transcripts could be upregulated by sixfold after stimulation with the T cell-derived cytokine IFN-gamma. Treatment with a diet deficient in essential fatty acids (which attenuates arteriosclerosis) or CTLA-4 Ig (which blocks lymphocyte activation) significantly decreased AIF-1 transcript levels. Upregulation of AIF-1 in the setting of T cell activation suggests that it may play a role in macrophage activation and function.
Effects of clofibrate and sulfinpyrazone on platelet survival time in coronary artery disease.
Authors: P Steele, D Battock, E Genton
Journal: Circulation (1975)

Platelet survival time was measured (autologous labelling with 51chromium) in 68 men with coronary artery disease (CAD). Survival was shortened slightly (3.2 +/- 0.04 days; mean +/- SEM) as compared to normal (3.7 +/- 0.04 days; N = 18; P less than 0.001), and 60% had shortened survival (less than 3.3 days). Thirty-seven had hyperlipoproteinemia (36 with Type IV and one with Type III) and platelet survival was shortened (3.1 +/- 0.10 days) and significantly different from survival of men with normal lipoproteins (3.3 +/- 0,12 days; P less than 0.05). Twenty-two with shortened platelet survival and CAD received either clofibrate or sulfinpyrazone. Clofibrate prolonged platelet survival (2.6 +/- 0.09 to 3.4 +/- 0,14 days; P less than 0.001) and ten of 12 had prolongation of survival. Sulfinpyrazone increased survival (2.8 +/- 0.12 to 3.6 +/- 0.21; P less than 0.001) and nine of ten had prolognation of platelet survival. Clofibrate lowered serum cholesterol and tryglyceride but alteration in lipids did not correlate with alteration of survival. Sulfinpyrazone did not alter lipids. Data suggest that survival is shortened in CAD and that clofibrate and sulfinpyrazone alter survival. Platelet suppressant agents may prove beneficial in reducing the extent and complications of atherosclerotic arterial injury.