tbuckley/cabot-search huggingface dataset:
A role for p53 in terminal epithelial cell differentiation
Authors: Zubaida Saifudeen, Susana Dipp, Samir S. El-Dahr
Journal: Journal of Clinical Investigation (2002)

Terminal epithelial cell differentiation is a crucial step in development. In the kidney, failure of terminal differentiation causes dysplasia, cystogenesis, and cancer. The present study provides multiple lines of evidence implicating the tumor suppressor protein p53 in terminal differentiation of the renal epithelium. In the developing kidney, p53 is highly enriched in epithelial cells expressing renal function genes (RFGs), such as receptors for vasoactive hormones, the sodium pump, and epithelial sodium and water channels. In comparison, proliferating renal progenitors express little if any p53 or RFGs. p53 binds to and transactivates the promoters of RFGs. In contrast, expression of a dominant negative mutant form of p53 inhibits endogenous RFG expression. Moreover, binding of endogenous p53 to the promoters of RFGs coincides with the differentiation process and is attenuated once renal epithelial cells are fully differentiated. Finally, p53-null pups exhibit a previously unrecognized aberrant renal phenotype and spatial disorganization of RFGs. Interestingly, the p53-related protein p73 is unable to functionally compensate for the loss of p53 and fails to efficiently activate RFG transcription. We conclude that p53 promotes the biochemical and morphological differentiation of the renal epithelium. Aberrations in p53-mediated terminal differentiation may therefore play a role in the pathogenesis of nephron dysgenesis and dysfunction.
Dependence of temporal variability of ventricular recovery on myocardial fibrosis. Role of mechanoelectric feedback?
Authors: Donatella Stilli, Beatrice Aimi, Andrea Sgoifo, Patrizia Ciarlini, Giuseppe Regoliosi, Costanza Lagrasta, Giorgio Olivetti, Ezio Musso
Journal: Cardiovascular Research (1998)

Objective: The study was aimed at establishing the effect of factors involved in the expression of mechanoelectric feedback in the heart, such as R-R interval and connective tissue, on time dependent changes in ventricular recovery, as determined at the body surface by beat to beat variability of QRST integral maps (BBV-IM). Methods: We used 15 normal 6-month-old Wistar rats. In each anesthetized animal, we performed a 3-minute continuous recording of 44 simultaneous chest ECGs. The signals were interactively processed, 1) to determine mean R-R interval and R-R variability throughout the recording period and 2) to compute QRST integral maps from approximately 50 beats belonging to the end of expiration. Then BBV-IM was calculated and expressed as percentage of beats significantly differing from a template. At sacrifice, the amount of myocardial fibrosis was morphometrically evaluated. Results: R-R interval was 149 ms±4, R-R interval variability 0.008±0.001 and BBV-IM 30.7%±4.4. Myocardial fibrosis expressed as % volume of left ventricular myocardium, numerical density of fibrotic foci and average cross-sectional area of the foci was 3.0%±0.4, 3.8±0.6 and 4.4 μm2/1000±0.1 respectively. BBV-IM was positively correlated to the % volume of fibrosis (r = 0.81, P<0.0003). Both measurements were positively correlated to R-R interval (BBV-IM: r = 0.83, P<0.0001; % volume of fibrosis: r = 0.87, P<0.0001) and negatively correlated to cardiac weights (BBV-IM: r = −0.79, P<0.0005; % volume of fibrosis: r = −0.75, P<0.001). Conclusion: Beat to beat changes in ventricular repolarization attributable to mechanoelectric transduction can be detected at the body surface by means of BBV-IM.
Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial
Authors: David J Kuter, James B Bussel, Roger M Lyons, Vinod Pullarkat, Terry B Gernsheimer, Francis M Senecal, Louis M Aledort, James N George, Craig M Kessler, Miguel A Sanz, Howard A Liebman, Frank T Slovick, J Th M de Wolf, Emmanuelle Bourgeois, Troy H Guthrie, Adrian Newland, Jeffrey S Wasser, Solomon I Hamburg, Carlos Grande, François Lefrère, Alan Eli Lichtin, Michael D Tarantino, Howard R Terebelo, Jean-François Viallard, Francis J Cuevas, Ronald S Go, David H Henry, Robert L Redner, Lawrence Rice, Martin R Schipperus, D Matthew Guo, Janet L Nichol
Journal: The Lancet (2008)
The interrelationships of pancreatic enzymes in human duodenal aspirate
Authors: D. M. Goldberg, K. G. Wormsley
Journal: Gut (1970)

The interrelationships of proteolytic enzymes and amylase have been studied in the duodenal aspirate obtained from subjects with normal and abnormal pancreatic function during stimulation with secretin and pancreozymin. While the relationship of trypsin to chymotrypsin was independent of stimulus and presence of pancreatic disease the ratio of proteolytic enzymes to amylase rose when the degree of stimulation of the pancreas was increased. Patients with recent acute pancreatitis and with chronic pancreatitis tended to have more severe impairment of secretion of proteolytic enzymes than of amylase. In routine tests of pancreatic function both proteolytic and non-proteolytic enzymes should be measured, both because an abnormal ratio may be of diagnostic significance and because the two different groups of enzymes provide mutual checks of the secretory capacity of pancreatic enzymes.
Supporting Those Who Go to Fight Ebola
Authors: Michelle M. Mello, Maria W. Merritt, Scott D. Halpern
Journal: PLoS Medicine (2015)

The Ebola epidemic is testing virtually every aspect of the public health and health care systems in the United States, including health care institutions' public service commitments.Although the number of cases in the US remains very small, an extraordinary amount of public and hospital resources have been devoted to preparing for new cases domestically [1][2][3][4].In contrast, although US hospital and medical professional organizations have called for an "enhanced focus" on containing Ebola in West Africa [5], there is a striking absence of public commitments on the part of US health care institutions to contribute to the containment effort.By quickly mobilizing qualified health care professionals (HCPs) to work in Guinea, Liberia, and Sierra Leone, US hospitals could not only meet the needs of desperate patients, but could contain Ebola at its source, averting global risk [6].Yet, US institutions' response to the West African epidemic has been muted thus far.Reports indicate that many institutions-even those with a tradition of sending personnel to respond to other humanitarian crises-have asked their HCPs to stay home this time [7][8][9].Although some academic medical centers (AMCs) in the US have invoked their usual policy that the university will support overseas work with services such as emergency travel assistance, others have specified that staff who serve in Ebola-affected regions do so in their personal capacity, not as employees.Still others have strongly cautioned against serving, prohibited official travel to affected regions, required staff to take vacation time or unpaid leave for 21 days following repatriation before returning to work, and made clear that the university will not assist if the HCP falls ill.The concerns that may motivate hospitals to discourage volunteers do not outweigh the countervailing considerations.At a minimum, institutions ought not to impede service; ideally, they would promote it.
Longitudinal Analysis of Sexual Function Reported by Men in the Prostate Cancer Prevention Trial
Authors: C. M. Moinpour, A. K. Darke, G. W. Donaldson, I. M. Thompson, C. Langley, D. P. Ankerst, D. L. Patrick, J. E. Ware, P. A. Ganz, S. A. Shumaker, S. M. Lippman, C. A. Coltman
Journal: JNCI Journal of the National Cancer Institute (2007)

The Prostate Cancer Prevention Trial (PCPT) was a randomized, double-blind, placebo-controlled study of the efficacy of finasteride in preventing prostate cancer in 18882 men aged 55 years or older. The PCPT offered an opportunity to prospectively study the effects of finasteride and other covariates on sexual dysfunction. We assessed sexual dysfunction in 17313 PCPT participants during a 7-year period. A battery of questionnaires assessed sexual dysfunction (Sexual Activity Scale score); age; race; SF-36 Mental Health Inventory-5, Physical Function, and Vitality scores; body mass index; smoking status; and the presence of diabetes and hypertension. Assessments began at month 6 after random assignment and included the Sexual Activity Scale score at randomization as a covariate. Two-sided general t tests, with a cutoff of P value less than .05, were used to determine the statistical significance for mixed model effects with correlated random time slopes and intercepts. The changing impact of covariates on sexual dysfunction was also assessed at 6 months, 3.5 years, and 6.5 years after randomization. Finasteride increased sexual dysfunction only slightly and its impact diminished over time; the increase in the Sexual Activity Scale score relative to placebo of 3.21 points (95% confidence interval [CI] = 2.83 to 3.59 points; P <.001) at the first assessment decreased to 2.11 points (95% CI = 1.44 to 2.81 points; P <.001) at the end of study. These Sexual Activity score values were small on a scale of 0–100, the range observed in the study, and in comparison with individual variation. After adjustment for all covariates, mean sexual dysfunction increased in both arms from baseline (6 months after randomization) by 1.26 Sexual Activity points (95% CI = 1.16 to 1.36 points; P <.001) per year, corresponding to a cumulative increase of 8.22 points (95% CI = 7.52 to 8.92 points; P <.001) over the study period. The effect of finasteride on sexual functioning is minimal for most men and should not impact the decision to prescribe or take finasteride.
Prooxidative effects of nitroglycerin in hyperlipidemic animals: oxidative stress in vasculature as an initiating event leading to impaired endothelial relaxation and increased plasma oxidation
Authors: T. Heltzer, A. Kontush, R. Mecharzina, T. Möller-Bertram, D. Lavall, B. Freeman, U. Beislegel, T. Melnertz, T. Münzel
Journal: Journal of the American College of Cardiology (1998)
INDEPENDENCE OF <i>H</i>-2<i>K</i> AND <i>H</i>-2<i>D</i> ANTIGENIC DETERMINANTS ON THE SURFACE OF MOUSE LYMPHOCYTES
Authors: Catherine Neauport-Sautes, Frank Lilly, Danielle Silvestre, François M. Kourilsky
Journal: The Journal of Experimental Medicine (1973)

At 37 degrees C, fluorescein-conjugated anti-H-2 alloantibodies specifically induce, at the surface of living mouse lymphocytes, the redistribution of the corresponding H-2 antigens, which cluster as patches and sometimes single caps at one pole of the cell. This aggregation is inhibited at 0 degrees C and the H-2 antigens, stained by fluorescent antibodies in the cold, appear evenly spread over the cell surface. This phenomenon was used to define the relationships between the membrane structures bearing the antigens coded by the H-2K and the H-2D genes of the H-2 region. Monospecific anti-H-2 antibodies coupled to either tetramethyl rhodamine isothiocyanate or fluorescein isothiocyanate were used to induce the redistribution of H-2D and H-2K antigens of the H-2(b) and H-2(k) haplotype at the surface of lymph node cells from homozygous and F(1) hybrid mice. It was observed that the diffuse distribution of H-2K antigens labeled at 0 degrees C was not affected by the prior antibody-induced aggregation of H-2D antigens and vice versa. The results were the same for H-2 antigens governed by genes located either in cis or in trans position. These data indicate that the H-2K and H-2D antigens migrate independently at the cell surface, and suggest that the gene products from the D and the K end of the H-2 region are expressed on independent molecules or structures at the cell membrane.
TRUNK AND GLUTEUS-MEDIUS MUSCLES' FATIGABILITY DURING OCCUPATIONAL STANDING IN CLINICAL INSTRUCTORS WITH LOW BACK PAIN
Authors: Eman Embaby, Amira Abdallah
Journal: British Journal of Sports Medicine (2013)

Background Occupational standing is associated with low back pain (LBP) development. Yet, trunk and gluteus-medius muscles' fatigability has not been extensively studied during occupational standing. This study examined and correlated the rectus abdominus (RA), erector-spinae (ES), external oblique (EO), and gluteus-medius (GM) muscles' fatigability on both sides while standing in a confined area for 30 min. Methods Median frequency EMG data were collected from 15 female clinical instructors with chronic LBP (group A) and 15 asymptomatic controls (group B) (mean age 29.53±2.4 vs 29.07±2.4 years, weight 63.6±7 vs 60±7.8kg, and height 162.73±4 vs 162.8±6 cm respectively) using a spectrum analysis program. Data were collected in the first and last 5 min of the standing task. Results Using Mixed three-way ANOVA, groupA showed significantly (p&lt;0.05) lower frequencies for the right and left ES, and right GM in the last 5min and significantly higher frequencies for the left RA in the first and last 5min than group B. In addition, the left ES and right EO, ES and GM in group B showed significantly higher frequencies and the left ES in groupA showed significantly lower frequencies in the last 5 min compared with the first. Moreover, the right RA showed significantly higher frequencies than the left in the last 5 min in groupB. Finally, there were significant (p&lt;0.05) correlations among the median frequencies of the tested four muscles on the same side and between both sides in both groups. Discussion/Conclusions Clinical instructors with LBP are more liable to have higher trunk and gluteus-medius muscle fatigue than asymptomatic individuals. Thus, endurance training for these muscles should be included in the rehabilitation of such patients.Key words: Fatigability, Trunk, Gluteus-medius, EMG, Standing, LBP
No reliable gender differences in attachment across the lifespan
Authors: Marian J. Bakermans-Kranenburg, Marinus H. van IJzendoorn
Journal: Behavioral and Brain Sciences (2009)

Abstract In middle childhood, boys show more avoidant attachments and girls more ambivalent attachments as a prelude to gender differentiation in reproductive strategies. However, we have failed to find systematic and method-independent gender differences in middle or late childhood attachments, nor in adult attachment representations. We conclude that Del Giudice's model rests on a brittle empirical basis.
Loss of H3K4 methylation destabilizes gene expression patterns and physiological functions in adult murine cardiomyocytes
Authors: Adam B. Stein, Thomas A. Jones, Todd J. Herron, Sanjeevkumar R. Patel, Sharlene M. Day, Sami F. Noujaim, Michelle L. Milstein, Matthew Klos, Philip B. Furspan, José Jalife, Gregory R. Dressler
Journal: Journal of Clinical Investigation (2011)

Histone H3 lysine 4 (H3K4me) methyltransferases and their cofactors are essential for embryonic development and the establishment of gene expression patterns in a cell-specific and heritable manner. However, the importance of such epigenetic marks in maintaining gene expression in adults and in initiating human disease is unclear. Here, we addressed this question using a mouse model in which we could inducibly ablate PAX interacting (with transcription-activation domain) protein 1 (PTIP), a key component of the H3K4me complex, in cardiac cells. Reducing H3K4me3 marks in differentiated cardiomyocytes was sufficient to alter gene expression profiles. One gene regulated by H3K4me3 was Kv channel-interacting protein 2 (Kcnip2), which regulates a cardiac repolarization current that is downregulated in heart failure and functions in arrhythmogenesis. This regulation led to a decreased sodium current and action potential upstroke velocity and significantly prolonged action potential duration (APD). The prolonged APD augmented intracellular calcium and in vivo systolic heart function. Treatment with isoproterenol and caffeine in this mouse model resulted in the generation of premature ventricular beats, a harbinger of lethal ventricular arrhythmias. These results suggest that the maintenance of H3K4me3 marks is necessary for the stability of a transcriptional program in differentiated cells and point to an essential function for H3K4me3 epigenetic marks in cellular homeostasis.
Noninvasive Ventilation Improves Preoxygenation before Intubation of Hypoxic Patients
Authors: Christophe Baillard, Jean-Philippe Fosse, Mustapha Sebbane, Gérald Chanques, Francçois Vincent, Patricia Courouble, Yves Cohen, Jean-Jacques Eledjam, Frédéric Adnet, Samir Jaber
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Critically ill patients are predisposed to oxyhemoglobin desaturation during intubation.Objectives: To find out whether noninvasive ventilation (NIV), as a preoxygenation method, is more effective at reducing arterial oxyhemoglobin desaturation than usual preoxygenation during orotracheal intubation in hypoxemic, critically ill patients.Methods: Prospective randomized study performed in two surgical/medical intensive care units (ICUs). Preoxygenation was performed, before a rapid sequence intubation, for a 3-min period using a nonrebreather bag-valve mask (control group) or pressure support ventilation delivered by an ICU ventilator through a face mask (NIV group) according to the randomization.Measurements and Main Results: The control (n = 26) and NIV (n = 27) groups were similar in terms of age, disease severity, diagnosis at admission, and pulse oxymetry values (SpO2) before preoxygenation. At the end of preoxygenation, SpO2 was higher in the NIV group as compared with the control group (98 ± 2 vs. 93 ± 6%, p < 0.001). During the intubation procedure, the lower SpO2 values were observed in the control group (81 ± 15 vs. 93 ± 8%, p < 0.001). Twelve (46%) patients in the control group and two (7%) in the NIV group had an SpO2 below 80% (p < 0.01). Five minutes after intubation, SpO2 values were still better in the NIV group as compared with the control group (98 ± 2 vs. 94 ± 6%, p < 0.01). Regurgitations (n = 3; 6%) and new infiltrates on post-procedure chest X ray (n = 4; 8%) were observed with no significant difference between groups.Conclusion: For the intubation of hypoxemic patients, preoxygenation using NIV is more effective at reducing arterial oxyhemoglobin desaturation than the usual method.
Pulmonary aplasia--a quantitative analysis of the development of the single lung
Authors: D. Ryland, L. Reid
Journal: Thorax (1971)

Quantitative studies have, for the first time, been carried out on the single lung in a case of unilateral pulmonary aplasia, in which the other lung was represented by a rudimentary bronchial stump. The patient died at the age of 3 months. The lung was enlarged to almost twice the normal volume, filling the intrathoracic cavity. The bronchial generations were reduced in number. Pulmonary artery branches were also too few, the supernumerary being more reduced than the conventional; muscle had extended abnormally far into peripheral arteries. The alveolar number was twice the normal for one lung, that is, it represented the normal total for age; alveolar size was rather less than normal. The hypoplasia of airways and blood vessels represents an early intrauterine disturbance in lung growth, caused perhaps by the same factor that inhibited the development of the second lung; the increased alveolar multiplication probably reflects increase in available space during fetal life.
Sympathetic discharge to mesenteric organs and the liver. Evidence for substantial mesenteric organ norepinephrine spillover.
Authors: A Aneman, G Eisenhofer, L Olbe, J Dalenbäck, P Nitescu, L Fändriks, P Friberg
Journal: Journal of Clinical Investigation (1996)

This study using sampling of blood from the portal vein, in addition to arterial and hepatic sites, to estimate separately spillovers of norepinephrine from mesenteric organs and the liver in seven patients undergoing upper abdominal surgery. Conventional measurements in arterial and hepatic venous plasma provided a measure of net hepatomesenteric NE spillover (403 pmol/ml) that indicated a 13% contribution of these organs to total body spillover of NE into systemic plasma (3,071+/-518 pmol/min). The net hepatomesenteric spillover of NE into systemic plasma was much lower than the spillover of NE from mesenteric organs into portal venous plasma (1,684+/-418 pmol/min). This and the hepatic spillover of NE into systemic plasma (212+/-72 pmol/min) indicated a considerable combined spillover of NE from hepatomesenteric organs (1,896+/-455 pmol/min). The sum of the latter estimate with the difference between total body and net hepatomesenteric NE spillovers provided an adjusted total body spillover of NE into both systemic and portal venous plasma (4,564+/-902 pmol/min). Mesenteric organs made a 37% contribution, and the liver made a 5% contribution to the adjusted total body spillover of NE. Thus, a substantial proportion of total body sympathetic outflow is directed towards mesenteric organs; this is obscured by efficient hepatic extraction of NE (86+/-6%) when measurements are restricted to arterial and hepatic venous plasma.
Impact of Hospice Disenrollment on Health Care Use and Medicare Expenditures for Patients With Cancer
Authors: Melissa D.A. Carlson, Jeph Herrin, Qingling Du, Andrew J. Epstein, Colleen L. Barry, R. Sean Morrison, Anthony L. Back, Elizabeth H. Bradley
Journal: Journal of Clinical Oncology (2010)

Patients with cancer represent the largest diagnostic group of hospice users, with 560,000 referred for hospice in 2008. Oncologists rely on hospice teams to provide care for patients who have completed disease-directed treatment and desire to remain at home. However, 11% to 15% of hospice users disenroll from hospice, and little is known about their health care use and Medicare expenditures.We used Surveillance, Epidemiology and End Results-Medicare data for hospice users who died as a result of cancer between 1998 and 2002 (N = 90,826) to compare rates of hospitalization, emergency department, and intensive care unit admission and hospital death for hospice disenrollees and those who remained with hospice until death. We also compared per-day and total Medicare expenditures across the two groups.Patients with cancer who disenrolled from hospice were more likely to be hospitalized (39.8% v 1.6%; P < .001), more likely to be admitted to the emergency department (33.9% v 3.1%; P < .001) or intensive care unit (5.7% v 0.1%; P < .001), and more likely to die in the hospital (9.6% v 0.2%; P < .001). Patients who disenrolled from hospice died a median of 24 days following disenrollment, suggesting that the reason for hospice disenrollment was not improved health. In multivariable analyses, hospice disenrollees incurred higher per-day Medicare expenditures than patients who remained with hospice until death (higher per-day expenditures of $124; P < .001).Hospice disenrollment is a marker for higher health care use and expenditures for care. Strategies to manage a patient's care and support family caregivers following hospice disenrollment may be beneficial and should be explored.