tbuckley/cabot-search huggingface dataset:
Effect of Vasodilator Therapy on Mortality in Chronic Congestive Heart Failure
Authors: Jay N. Cohn, Donald G. Archibald, Susan Ziesche, Joseph A. Franciosa, W. Eugene Harston, Felix E. Tristani, W. Bruce Dunkman, William Jacobs, Gary S. Francis, Kathleen H. Flohr, Steven Goldman, Frederick R. Cobb, Pravin M. Shah, Robert Saunders, Ross D. Fletcher, Henry S. Loeb, Vincent C. Hughes, Bonnie Baker
Journal: New England Journal of Medicine (1986)

To evaluate the effects of vasodilator therapy on mortality among patients with chronic congestive heart failure, we randomly assigned 642 men with impaired cardiac function and reduced exercise tolerance who were taking digoxin and a diuretic to receive additional double-blind treatment with placebo, prazosin (20 mg per day), or the combination of hydralazine (300 mg per day) and isosorbide dinitrate (160 mg per day). Follow-up averaged 2.3 years (range, 6 months to 5.7 years). Mortality over the entire follow-up period was lower in the group that received hydralazine and isosorbide dinitrate than in the placebo group. This difference was of borderline statistical significance. For mortality by two years, a major end point specified in the protocol, the risk reduction among patients treated with both hydralazine and isosorbide dinitrate was 34 percent (P<0.028). The cumulative mortality rates at two years were 25.6 percent in the hydralazine–isosorbide dinitrate group and 34.3 percent in the placebo group; at three years, the mortality rate was 36.2 percent versus 46.9 percent. The mortality-risk reduction in the group treated with hydralazine and isosorbide dinitrate was 36 percent by three years. The mortality in the prazosin group was similar to that in the placebo group. Left ventricular ejection fraction (measured sequentially) rose significantly at eight weeks and at one year in the group treated with hydralazine and isosorbide dinitrate but not in the placebo or prazosin groups. Our data suggest that the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics in patients with chronic congestive heart failure can have a favorable effect on left ventricular function and mortality. (N Engl J Med 1986; 314:1547–52.)
Consistency Test of the Cell Cycle: Roles for p53 and EGR1
Authors: Yaara Zwang, Moshe Oren, Yosef Yarden
Journal: Cancer Research (2012)

Mammalian cells are constantly exposed to multiple mitogens and, hence, have developed machineries that help them ignore fortuitous signals. In a recent report in Molecular Cell, we highlighted the molecular details of such a noise-reduction filter, including roles for EGR1, AKT, and p53. Brief exposure to a mitogen drives formation of inhibitory p53-chromatin complexes, which are disabled only if the growth factor is still present several hours later. We propose that this "consistency test" prevents repeated division cycles of normal cells but might become defective in most cancer cells.
Association of Breast-feeding and Early Childhood Overweight in Children From Mothers With Gestational Diabetes Mellitus
Authors: U. M. Schaefer-Graf
Journal: Diabetes Care (2006)

Because of an exponential increase in childhood and adolescent obesity, its prevention has become a major health care goal (1). There is increasing evidence (2–4) that breast-feeding has a protective effect against obesity in later life. However, most studies investigating the effect of breast-feeding have not looked exclusively at infants of diabetic women (5).

Previous studies (6–8) reported a high risk of obesity in children of mothers who have diabetes during pregnancy. Reports pertaining to the effects of breast-feeding following a pregnancy complicated by diabetes have focused on the delay or prevention of the appearance of islet autoimmunity among children of mothers who have type 1 diabetes (9,10). Conflicting results have been reported from short-term observations regarding the effect of breast-feeding on obesity of offspring (11,12). There is a paucity of data in children of mothers who have gestational diabetes mellitus (GDM).

In a recent study (6) of infants of mothers who had GDM, we demonstrated that parental obesity and excessive intrauterine growth resulting in neonatal overweight independently contribute to early childhood obesity. In the present study, we assessed the association of breast-feeding during infancy and the prevalence of overweight in early life in the same cohort of children.

Women with GDM who were taken care of by the Diabetes Prenatal Care Clinic of Vivantes Medical Center from 1995 through 2000 were asked to return …
Pulmonary epithelial permeability in ARDS and cardiogenic pulmonary oedema
Authors: T Todisco, M Dottorini, F Rossi, A Baldoncini, R Palumbo
Journal: European Respiratory Journal (1988)

Clearance of inhaled 99mTechnetium-labelled diethylene triamine pentacetate (99mTc-DTPA) from the lung, an index of pulmonary alveolar epithelial permeability (PAEP), was measured in 13 patients with cardiogenic interstitial pulmonary oedema (CIPO) and in 7 patients with adult respiratory distress syndrome (ARDS). Thirty-five normal subjects (22 nonsmokers and 13 smokers) were evaluated as controls. Half-time clearance (t0.5) values in ARDS patients (mean +/- SD: 15 +/- 2 min) were significantly lower than in CIPO patients (62 +/- 9 min). This PAEP increase in ARDS was impressive, even in comparison to heavy smokers. Loss of the PAEP vertical gradient (apical PAEP greater than base PAEP) was observed in both cardiogenic and ARDS lungs and among smokers.
Signaling through IFN Regulatory Factor-5 Sensitizes p53-Deficient Tumors to DNA Damage–Induced Apoptosis and Cell Death
Authors: Guodong Hu, Margo E. Mancl, Betsy J. Barnes
Journal: Cancer Research (2005)

Abstract Human IFN regulatory factor-5 (IRF-5) is a candidate tumor suppressor gene that mediates cell arrest, apoptosis, and immune activation. Here we show that ectopic IRF-5 sensitizes p53-proficient and p53-deficient colon cancer cells to DNA damage–induced apoptosis. The combination IFN-β and irinotecan (CPT-11) cooperatively inhibits cell growth and IRF-5 synergizes with it to further promote apoptosis. The synergism is due to IRF-5 signaling since a striking defect in apoptosis and cell death was observed in IRF-5-deficient cells, which correlated well with a reduction in DNA damage–induced cellular events. Components of this IRF-5 signaling pathway are investigated including a mechanism for DNA damage–induced IRF-5 activation. Thus, IRF-5–regulated pathways may serve as a target for cancer therapeutics.
NE-10 Neuroendocrine Cancer Promotes the LNCaP Xenograft Growth in Castrated Mice
Authors: Ren Jie Jin, Yongqing Wang, Naoya Masumori, Kenichiro Ishii, Taiji Tsukamoto, Scott B. Shappell, Simon W. Hayward, Susan Kasper, Robert J. Matusik
Journal: Cancer Research (2004)

Abstract Increases in neuroendocrine (NE) cells and their secretory products are closely correlated with tumor progression and androgen-independent prostate cancer. However, the mechanisms by which NE cells influence prostate cancer growth and progression, especially after androgen ablation therapy, are poorly understood. To investigate the role of NE cells on prostate cancer growth, LNCaP xenograft tumors were implanted into nude mice. After the LNCaP tumors were established, the NE mouse prostate allograft (NE-10) was implanted on the opposite flank of these nude mice to test whether NE tumor-derived systemic factors can influence LNCaP growth. Mice bearing LNCaP tumors with or without NE allografts were castrated 2 weeks after NE tumor inoculation, and changes in LNCaP tumor growth rate and gene expression were investigated. After castration, LNCaP tumor growth decreased in mice bearing LNCaP tumors alone, and this was accompanied by a loss of nuclear androgen receptor (AR) localization. In contrast, in castrated mice bearing both LNCaP and NE-10 tumors, LNCaP tumors continued to grow, had increased levels of nuclear AR, and secreted prostate-specific antigen. Therefore, in the absence of testicular androgens, NE secretions were sufficient to maintain LNCaP cell growth and androgen-regulated gene expression in vivo. Furthermore, in vitro experiments showed that NE secretions combined with low levels of androgens activated the AR, an effect that was blocked by the antiandrogen bicalutamide. Because an increase in AR level has been reported to be sufficient to account for hormone refractory prostate cancers, the NE cell population ability to increase AR level/activity can be another mechanism that allows prostate cancer to escape androgen ablation therapy.
Mechanisms of Pulmonary Fibrosis
Authors: Victor J. Thannickal, Galen B. Toews, Eric S. White, Joseph P. Lynch III, Fernando J. Martinez
Journal: Annual Review of Medicine (2004)

Tissue injury evokes highly conserved, tightly regulated inflammatory responses and less well-understood host repair responses. Both inflammation and repair involve the recruitment, activation, apoptosis, and eventual clearance of key effector cells. In this review, we propose the concept of pulmonary fibrosis as a dysregulated repair process that is perpetually "turned on" even though classical inflammatory pathways may be dampened or "switched off." Significant regional heterogeneity, with varied histopathological patterns of inflammation and fibrosis, has been observed in individual patients with idiopathic pulmonary fibrosis. We discuss environmental factors and host response factors, such as genetic susceptibility and age, that may influence these varied manifestations. Better understanding of the mechanisms of lung repair, which include alveolar reepithelialization, myofibroblast differentiation/activation, and apoptosis, should offer more effective therapeutic options for progressive pulmonary fibrosis.
Accuracy, precision and linearity of the portable flow-volume meter Microspiro HI-298
Authors: E Dompeling, CP van Schayck, H Folgering, HJ van den Hoogen, C van Weel
Journal: European Respiratory Journal (1991)

The accuracy, precision and linearity of a new portable flow-volume meter, the Microspiro HI-298 (Chest Corporation, Tokyo, Japan), was investigated using a Fleisch no. 4 pneumotachograph as a standard. After connection and calibration of the pneumotachograph and the Microspiro, a healthy subject performed 44 forced vital capacity (FVC) manoeuvres at different levels of lung inflation. The FVC of these expirations ranged from 2.5-5.1 l. Linear regression of Microspiro values (dependent variable) on Fleisch pneumotachograph values (independent variable) showed that a good linear relationship existed: Pearson correlation coefficients ranged from 0.938-0.985. Linearity of the Microspiro was good except for the peak expiratory flow rate (PEFR) and the maximal expiratory flow at 25% of the expired volume (MEF75). The random error (measure of precision) of all flow-volume (F-V) indices was lower than 5%. The systematic error (measure of accuracy) was low for the forced expiratory volume in one second (FEV1) and the FVC (1% and 4.6%, respectively) but much higher for the instantaneous expiratory flows (PEFR 11.0%; MEF75 7.0%; MEF50 8.5%; MEF25 11.4%). Only the total error in FEV1 complied with the tolerance of 4% of the European Community for Coal and Steel (ECCS). When the measured values were adjusted according to the regression equations of this study, all F-V indices were accurate and precise within 5%. It was concluded that the portable Microspiro HI-298 is a useful instrument for bedside, work-site spirometry and for use in general practice.(ABSTRACT TRUNCATED AT 250 WORDS)
Oral squamous cell carcinoma Mouthwashes may increase risk
Authors: J Llewelyn
Journal: BMJ (1994)

cerebral palsy and those who died, but the increased risk of suboptimal care in these groups remained after adjustment for this.To carry out the analysis that Hall suggests and still retain our matched design, much larger numbers would have been needed.To explore further the complex interrelation of antenatal and intrapartum factors, care, and cerebral palsy, collaborative studies will be necessary.
Neuropsychiatric systemic lupus erythematosus
Authors: D. ISENBERG, E. CRAWLEY, P. WOO;, M J ROOD, T W J HUIZINGA
Journal: Annals of the Rheumatic Diseases (1999)

Cladribine in the treatment of systemic lupus erythematosus nephritisSystemic lupus erythematosus (SLE) nephritis often requires treatment with cyclophosphamide, which carries the risk of major side eVects including infection, ovarian failure and bladder malignancy.Therapeutic strategies that would specifically target lymphocytes are appealing.Following the first report of the use of the purine nucleoside analogue cladribine (2-chloro-2'deoxyadenosine), a selective lymphocyte depleting agent, in the treatment of lupus nephritis, 1 we report our experience in two patients with severe renal involvement.
Stem Cell-Derived Cardiomyocytes Demonstrate Arrhythmic Potential
Authors: Ying Ming Zhang, Criss Hartzell, Michael Narlow, Samuel C. Dudley
Journal: Circulation (2002)

Background— Cardiomyocytes (CMs) derived from pluripotent embryonic stem cells (ESCs) and embryonal carcinoma cells (ECCs) have some but not all characteristics of adult myocytes. ESCs have shown the ability to engraft in areas of myocardial damage, which suggests their use in cell transplantation therapy for cardiomyopathy. We studied the arrhythmogenic properties of CMs differentiated from mouse ESCs and ECCs. Methods and Results— CMs derived in vitro were studied in the whole-cell patch-clamp mode. CMs from both sources showed action potential (AP) morphology heterogeneity, with reduced maximum upstroke velocities (dV/dt) and prolonged AP durations. CMs demonstrated prolonged, spontaneous electrical activity in culture. Frequent triggered activity was observed with and without pharmacological enhancement. Phase 2 or 3 early afterdepolarizations could be induced easily by Bay K8644 plus tetraethylammonium chloride (TEA) or [TEA] o after Cs + replacement for [K + ] i , respectively. A combination of bradycardic stimulation, hypokalemia, and quinidine resulted in early afterdepolarizations. Delayed afterdepolarizations could be induced easily and reversibly by hypercalcemia or isoproterenol. Conclusions— ESCs or ECCs differentiated into at least 3 AP phenotypes. CMs showed spontaneous activity, low dV/dt, prolonged AP duration, and easily inducible triggered arrhythmias. These findings raise caution about the use of totipotent ESCs in cell transplantation therapy, because they may act as an unanticipated arrhythmogenic source from any of the 3 classic mechanisms (reentry, automaticity, or triggered activity).
Prediction of incremental shuttle walking test in patients with chronic obstructive pulmonary disease
Authors: Kunihiko Anami, Jun Horie, Hiroyuki Naotsuka, Syuichi Shiranita, Shinichiro Hayashi
Journal: European Respiratory Journal (2013)

Purpose: In primary care, testing of formal exercise capacity is not always feasible. Therefore, we have created a formula to predict incremental shuttle walking test (ISWT) using the 30 seconds chair stand-up test (CS-30) (Takagawa, A. et al. The Journal of the Japan Society for Respiratory Care and Rehabilitation 2010: 20:156-159. in Japanese). The purpose of this study was to create a prediction equation ISWT in practice time and limited space in patients with chronic obstructive pulmonary disease (COPD).  Participants and methods: Subjects with stable men COPD were recruited (n = 115; mean ± SD age, 72.7 ± 8.1 years). We measured Body mass index (BMI), modified medical research council (mMRC) dyspnea scale, %FVC, %FEV1.0, CS-30, quadriceps strength, 6-munites walking test (6MWT), timed up and go test (TUG), St. gorge’s respiratory questionnaire (SGRQ), and ISWT.  Results: Prediction was created by multiple regression analysis: ISWT pred = –88.2×(mMRC dyspnea scale) + 13.7×(CS-30) + 293.4 (R2 = 0.612, p   Conclusion: Our results suggest the potential for prediction for ISWT. Further work is warranted to determine the effects of pulmonary rehabilitation for exercise capacity in patients with COPD.
Immunobiology of Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Lisbeth A. Welniak, Bruce R. Blazar, William J. Murphy
Journal: Annual Review of Immunology (2006)

Allogeneic hematopoietic stem cell transplantation (HSCT) has evolved into an effective adoptive cellular immunotherapy for the treatment of a number of cancers. The immunobiology of allogeneic HSCT is unique in transplantation in that it involves potential immune recognition and attack between both donor and host. Much of the immunobiology of allogeneic HSCT has been gleaned from preclinical models and correlation with clinical observations. We review our current understanding of some of the issues that affect the success of this therapy, including host-versus-graft (HVG) reactions, graft-versus-host disease (GVHD), graft-versus-tumor (GVT) activity, and restoration of functional immunity to prevent transplant-related opportunistic infections. We also review new strategies to optimize the GVT and improve overall immune function while reducing GVHD and graft rejection.
The Impact of Acute Hypoglycemia on Neuropsychological and Neurometabolite Profiles in Children With Type 1 Diabetes
Authors: Debbie Rankins, R. Mark Wellard, Fergus Cameron, Ciara McDonnell, Elisabeth Northam
Journal: Diabetes Care (2005)

The impact of hypoglycemia on brain is a major factor influencing the clinical management of type 1 diabetes in children. The Diabetes Control and Complications Trial (1) has shown that intensive insulin treatment is the most effective strategy for preventing the microvascular complications of type 1 diabetes, but it is associated with a threefold increase in the incidence of severe hypoglycemia. Before implementing intensified treatments in children, it is important to define the impact on the developing central nervous system associated with the increased risk of hypoglycemia. This report presents three cases of previously well children with type 1 diabetes who were studied after their first episode of severe hypoglycemia with seizure. All case subjects underwent neuropsychological assessment and neuroimaging within 48 h of the seizure and again 6 months later.

Case 1 was a 7-year-old girl with a 2-year history of type 1 diabetes who presented to the emergency department, Royal Children’s Hospital, following a severe hypoglycemic event with seizure. She awoke with a blood glucose level of 3.6 mmol/l. This was not treated, and she was given her usual morning dose of short- and intermediate-acting insulin. She had a seizure within 20 min of insulin administration. The seizure resolved within 5 min after treatment with glucagon and glucose gel. Her most recent HbA1c (A1C) was 7.5%.

Case 2 was a 9-year-old girl with a 6-year history of type 1 diabetes who experienced a hypoglycemic seizure immediately before breakfast after a nocturnal supplemental dose of rapid-acting insulin. She was treated with glucagon, with seizure resolution within 5 min. Her blood glucose level immediately after glucagon administration was 2.4 mmol/l. Her most recent A1C was 8.7%.

Case 3 was a 10-year-old boy with a 3-year history of type 1 diabetes who felt unwell for several days …
Myeloma Cells Are Highly Sensitive to the Granule Exocytosis Pathway Mediated by WT1-Specific Cytotoxic T Lymphocytes
Authors: Taichi Azuma, Takemi Otsuki, Kiyotaka Kuzushima, Christopher J. Froelich, Shigeru Fujita, Masaki Yasukawa
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Because WT1 is a universal tumor antigen, we examined the sensitivity of myeloma cells to WT1-specific cytotoxic T lymphocyte (CTL)-mediated cytotoxicity. Experimental Design: WT1 expression in hematologic malignant cells was examined by quantitative reverse transcription-polymerase chain reaction. The cytotoxicity of a WT1-specific CTL clone against hematologic malignant cells, including myeloma cells, was examined by standard chromium-51 release assays. The extent of membrane damage induced by purified perforin was examined. Induction of WT1-specific CTLs from the patients with multiple myeloma (MM) was attempted, and we examined their function against myeloma cells. Results: The expression levels of WT1 mRNA in myeloma and lymphoma cells were significantly lower than that in acute leukemia cells. Although the WT1 expression levels in myeloma and lymphoma cells were almost same, only myeloma cells were lysed efficiently by WT1-specific CTLs in a HLA-restricted manner. The amounts of interferon-γ produced by WT1-specific CTLs in response to stimulation with myeloma cells and with lymphoma cells were almost the same, suggesting that WT1 protein is processed and expressed in the context of HLA class I molecules similarly on both myeloma and lymphoma cells. The extent of membrane damage induced by purified perforin appeared to be significantly higher in myeloma cells than in lymphoma cells. WT1-specific CTLs appeared to be present in patients with MM. Conclusions: The present study has shown that susceptibility of membranes to perforin is an important factor determining the sensitivity of target cells to CTL-mediated cytotoxicity and that WT1 is an ideal target antigen for cellular immunotherapy of MM.
Resistance to CYP17A1 Inhibition with Abiraterone in Castration-Resistant Prostate Cancer: Induction of Steroidogenesis and Androgen Receptor Splice Variants
Authors: Elahe A. Mostaghel, Brett T. Marck, Stephen R. Plymate, Robert L. Vessella, Stephen Balk, Alvin M. Matsumoto, Peter S. Nelson, R. Bruce Montgomery
Journal: Clinical Cancer Research (2011)

Abiraterone is a potent inhibitor of the steroidogenic enzyme CYP17A1 and suppresses tumor growth in patients with castration-resistant prostate cancer (CRPC). The effectiveness of abiraterone in reducing tumor androgens is not known, nor have mechanisms contributing to abiraterone resistance been established.We treated human CRPC xenografts with abiraterone and measured tumor growth, tissue androgens, androgen receptor (AR) levels, and steroidogenic gene expression versus controls.Abiraterone suppressed serum PSA levels and improved survival in two distinct CRPC xenografts: median survival of LuCaP35CR improved from 17 to 39 days (HR = 3.6, P = 0.0014) and LuCaP23CR from 14 to 24 days (HR = 2.5, P = 0.0048). Abiraterone strongly suppressed tumor androgens, with testosterone (T) decreasing from 0.49 ± 0.22 to 0.03 ± 0.01 pg/mg (P < 0.0001), and from 0.69 ± 0.36 to 0.03 ± 0.01 pg/mg (P = 0.002) in abiraterone-treated 23CR and 35CR, respectively, with comparable decreases in tissue DHT. Treatment was associated with increased expression of full-length AR (AR(FL)) and truncated AR variants (AR(FL) 2.3-fold, P = 0.008 and AR(del567es) 2.7-fold, P = 0.036 in 23 CR; AR(FL) 3.4-fold, P = 0.001 and AR(V7) 3.1-fold, P = 0.0003 in 35CR), and increased expression of the abiraterone target CYP17A1 (∼2.1-fold, P = 0.0001 and P = 0.028 in 23CR and 35CR, respectively) and transcript changes in other enzymes modulating steroid metabolism.These studies indicate that abiraterone reduces CRPC growth via suppression of intratumoral androgens and that resistance to abiraterone may occur through mechanisms that include upregulation of CYP17A1, and/or induction of AR and AR splice variants that confer ligand-independent AR transactivation.