tbuckley/cabot-search huggingface dataset:
Looking down the atrioventricular canal
Authors: D. W. Benson, K. L. Sund
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Down's syndrome-like cardiac developmental defects in embryos of the transchromosomic Tc1 mouse’ by L. Dunlevy et al ., pp. 287–295, this issue. 

Down's syndrome (DS) is the most common aneuploidy diagnosed in liveborn babies (∼1/700 live births). While DS is typically associated with recognizable dysmorphic features, clinical anomalies exhibit variable expressivity. The DS phenotype includes many organ systems and affects all three embryonic germ layers. DS is the most frequent chromosomal cause of mental retardation, is a recognized genetic aetiology of Alzheimer disease, and is associated with congenital anomalies of the gastrointestinal and cardiac systems.1 It has been over 50 years since trisomy 21 was discovered as the genetic aetiology of DS.2 Despite progress in diagnosis and management of DS-related health problems, the definition of the pathogenetic mechanisms by which these gene dosage errors induce the DS phenotype and elucidation of DS genotype–phenotype correlations remains elusive. One of the barriers to progress in defining the underlying pathogenesis of this common genetic disorder has been the lack of a suitable animal model (reviewed in refs.3,4). This has been especially true for DS-associated cardiovascular malformations. Nearly half of the DS patients have a congenital heart malformation;5 the signature cardiac defect is atrioventricular septal defect (AVSD), also known as atrioventricular (AV) canal defect or endocardial cushion defect.6,7 The paper by Dunlevy et al .8 in the … 

*Corresponding author. Tel: +1 513 636 0389; fax: +1 513 636 5958, Email: woody.benson{at}cchmc.org
Raynaud's syndrome.
Authors: V F Challenor, K Donaldson, D G Waller
Journal: BMJ (1990)

<h3>Abstract</h3> Gene body methylation (GBM) is an ancestral form of DNA methylation whose role in development has remained unclear. Unlike vertebrates, DNA methylation is found exclusively in gene bodies in the wasp <i>Nasonia vitripennis</i>, which provides a unique opportunity to interpret the role of GBM in development. We confirmed that parental RNAi (pRNAi) knockdown of a DNMT1 ortholog (<i>Nv-Dnmt1a</i>) in <i>Nasonia</i> leads to embryonic lethality and failures in cellularization and morphogenesis. Using whole-genome bisulfite sequencing, we found a widespread loss of GBM in <i>Nv-Dnmt1a</i> pRNAi embryos. Using RNAseq, we found that methylated genes that lost GBM in the pRNAi samples were exclusively downregulated during zygotic genome activation. Unexpectedly, nearly all affected unmethylated genes were up-regulated after pRNAi. Lack of proper clearance of mRNAs and abnormal activation drive this up-regulation, indicating critical roles for <i>Nv-Dnmt1a</i> and GBM in the maternal-zygotic transition (MZT) in the wasp, despite their absence in <i>Drosophila</i>.
A CASE OF ADDISON'S DISEASE
Authors: H. S. Stannus
Journal: BMJ (1933)

IMEDICAL JOURNAL- investigations.Gordon discovered that when extracts made from glands taken from cases of Hodgkin's disease are injected intracerebrally into rabbits, symptoms of en- cephalitis are regularly produced.Although Gordon failed to transmit the disease from rabbit to rabbit he believes that his experiments demonstrate the virus nature of Hodgkin's disease.In our rabbits the symptoms have closely resembled those observed by Gordon, but there are differences of a quantitative kind, and there are differences in the incubation period and clinical picture.Whether these differences are due simply to differences in material or in technique can be determined only by further inquiries.We refrain from theoretical discussion until it is settled whether or not encephalitis produced by lymph glands from cases of Hodgkin's disease is identical with that produced by normal human bone marrow.
Occupational Hazards to Hospital Personnel
Authors: WILLIAM B. PATTERSON
Journal: Annals of Internal Medicine (1985)

Hospital personnel are subject to various occupational hazards. Awareness of these risks, compliance with basic preventive measures, and adequate resources for interventions are essential components of an occupational health program. Physical, chemical, and radiation hazards; important infectious risks; and psychosocial problems prevalent in hospital workers are reviewed. A rational approach to managing and preventing these problems is offered.
Recruitment of some respiratory muscles during three maximal inspiratory manoeuvres.
Authors: S Nava, N Ambrosino, P Crotti, C Fracchia, C Rampulla
Journal: Thorax (1993)

A study was undertaken to determine the level of recruitment of the muscles used in the generation of respiratory muscle force, and to ascertain whether maximal diaphragmatic force and maximal inspiratory muscle force need to be measured by separate tests. The level of activity of three inspiratory muscles and one expiratory muscle during three maximal respiratory manoeuvres was studied: (1) maximal inspiration against a closed airway (Muller manoeuvre or maximal inspiratory pressure (MIP)); (2) maximal inspired manoeuvre followed by a maximal expiratory effort (combined manoeuvre); and (3) maximal inspiratory sniff through the nose (sniff manoeuvre).All the manoeuvres were performed from functional residual capacity. The gastric (PGA) and oesophageal (POES) pressures and their difference, transdiaphragmatic pressure (PDI), and the integrated EMG activity of the diaphragm (EDI), the sternomastoid (ESTR), the intercostal parasternals (ERIC), and the rectus abdominis muscles (ERA) were recorded.Mean (SD) PDI values for the Muller, combined, and sniff manoeuvres were: 127.6 (19.4), 162.7 (22.2), and 136.6 (24.8) cm H2O, respectively. The pattern of rib cage muscle recruitment (POES/PDI) was similar for the Muller and sniff manoeuvres (88% and 80% respectively), and was 58% in the combined manoeuvre, confirming data previously reported in the literature. Peak EDI amplitude was greater during the sniff manoeuvre in all subjects (100%) than during the combined (88.1%) and Muller (61.1%) manoeuvres. ESTR and EIC were more active in the Muller and the sniff manoeuvres. The contribution of the expiratory muscle (ERA) to the three manoeuvres was 100% in the combined, 26.1% for the sniff, and 11.5% for the Muller manoeuvre.Each of these three manoeuvres results in different mechanisms of inspiratory and expiratory muscle activation and the intrathoracic and intra-abdominal pressures generated are a reflection of the interaction between the various muscle groups. The Muller and sniff manoeuvres reflect mainly the force of the inspiratory muscles and the combined manoeuvre that of the diaphragm.
ARMY PSYCHIATRIC LITERATURE, FACTORS IN INTERPRETATION
Authors: DAVID J. FLICKER
Journal: American Journal of Psychiatry (1942)

Some essential differences between the viewpoints of the civilian and army psychiatrists have been presented. Some of the problems and regulations which must be considered in interpreting literature that will be forthcoming concerning army psychiatry are herewith explained. It is hoped that this will prevent unwarranted generalizations or interpretations from a statistical standpoint and will enhance the value of the material.
Estradiol-Mediated Endothelial Nitric Oxide Synthase Association With Heat Shock Protein 90 Requires Adenosine Monophosphate-Dependent Protein Kinase
Authors: Eberhard Schulz, Elad Anter, Ming-Hui Zou, John F. Keaney
Journal: Circulation (2005)

Background— Estradiol activates endothelial nitric oxide synthase (eNOS) by mechanisms that involve estrogen receptor-α (ERα), protein kinase B/Akt, mitogen-activated protein kinases, and heat shock protein 90 (HSP90). Recently, AMP-activated protein kinase (AMPK), an enzyme that plays a crucial role in cellular adaptation to metabolic stress, has been implicated in physiological eNOS activation by the hormones adiponectin and insulin. We therefore investigated whether AMPK is activated by estradiol in endothelial cells and plays a role in estradiol-induced eNOS activation. Methods and Results— Porcine aortic endothelial cells exhibited time- and concentration-dependent AMPK activation as determined by phosphorylation of AMPK and its downstream target acetyl coenzyme A carboxylase in response to estradiol (1 nmol/L to 10 μmol/L, 1 to 30 minutes). AMPK activation by estradiol was independent of both AMP levels and ERα but required estradiol conversion to its catechol metabolites. Estradiol treatment increased eNOS catalytic activity, an effect that was largely reversed when endothelial cells were infected with an AMPK dominant-negative adenovirus. However, inhibition of AMPK did not alter estradiol-induced eNOS phosphorylation at serine 1177 or threonine 495 but decreased eNOS interaction with HSP90. Consistent with this observation, blood vessels from α 1 -AMPK-null mice exhibited defective eNOS-mediated NO production in response to estradiol. Conclusions— Taken together, these data indicate that AMPK activity is essential for estradiol-induced eNOS activation via the promotion of eNOS interaction with HSP90. These data point to a novel role for AMPK in modulating endothelial cell NO bioactivity and HSP90 function.
Myocardial Contusion Due to Steering Wheel Injury
Authors: Daniel Kahn
Journal: JAMA (1967)

IN the present age of high-speed automobile transport and increasing frequency of traffic accidents, one expects to encounter a growing number of chest injuries with cardiac involvement. Those of the direct, penetrating type are readily recognizable, but the nonpenetrating, indirect injuries to the heart may be overlooked. Early diagnosis is essential, not only because specific surgical treatment may be available for cardiac rupture or tamponade, but also because the management of myocardial contusion may be similar to that of myocardial infarction.  The first reported case of myocardial contusion due to nonpenetrating chest injury was described by Akenside 1 in 1763. A 14-year-old boy was struck in the chest by a plate. Autopsy six months later revealed extensive necrosis of the left ventricular wall, covered by adherent pericardium. Urbach 2 in 1940 found 185 cases of cardiac injury among 1,000 autopsy cases of chest contusion. From 1900 to 1937, 108 cases
Primary and Secondary Signaling Pathways in Early Preconditioning That Converge on the Mitochondria to Produce Cardioprotection
Authors: Elizabeth Murphy
Journal: Circulation Research (2004)

Cardioprotective mechanisms such as acute or early preconditioning activate several primary signaling pathways that seem to converge on mitochondrial targets, leading to altered cell metabolism and inhibition of apoptosis. Acute preconditioning leads to generation of agonists, which bind to G protein-coupled receptors, and initiates a signaling cascade that involves activation of phosphoinositide-3-kinase, endothelial NO synthase, protein kinase C, glycogen synthase kinase 3beta, mitogen-activated protein kinases, and other signaling pathways. Activation of these signaling pathways along with generation of reactive oxygen species leads to alterations in the activity of key mitochondrial proteins such as mitochondrial ATP-sensitive K(+) channels, the mitochondrial permeability transition pore, and bcl-2 family members. Alterations in these mitochondrial proteins results in altered metabolism and inhibition of cell death, thus resulting in cardioprotection.
Oncogenic Protein MTBP Interacts with MYC to Promote Tumorigenesis
Authors: Brian C. Grieb, Mark W. Gramling, Maria Pia Arrate, Xi Chen, Stephen L. Beauparlant, Dale S. Haines, Hua Xiao, Christine M. Eischen
Journal: Cancer Research (2014)

Despite its involvement in most human cancers, MYC continues to pose a challenge as a readily tractable therapeutic target. Here we identify the MYC transcriptional cofactors TIP48 and TIP49 and MYC as novel binding partners of Mdm2-binding protein (MTBP), a functionally undefined protein that we show is oncogenic and overexpressed in many human cancers. MTBP associated with MYC at promoters and increased MYC-mediated transcription, proliferation, neoplastic transformation, and tumor development. In breast cancer specimens, we determined overexpression of both MYC and MTBP was associated with a reduction in 10-year patient survival compared with MYC overexpression alone. MTBP was also frequently co-amplified with MYC in many human cancers. Mechanistic investigations implicated associations with TIP48/TIP49 as well as MYC in MTBP function in cellular transformation and the growth of human breast cancer cells. Taken together, our findings show MTBP functions with MYC to promote malignancy, identifying this protein as a novel general therapeutic target in human cancer.
Non-uniform recovery of segment shortening during reperfusion following regional myocardial ischaemia despite uniform recovery of ATP
Authors: H. Brunvand, S. E. Rynning, E. Hexeberg, J. Westby, K. Grong
Journal: Cardiovascular Research (1995)

This study focused on transmural postischaemic recovery of ATP and regional contractile function related to reversible and irreversible tissue injury.Fifty anaesthetised open-chest cats were randomised into two groups. Groups I: 10 min of LAD occlusion (n = 10) and 10 min of LAD occlusion followed by 180 min of reperfusion (n = 15). Group II: 40 min of LAD occlusion (n = 10) and 40 min of LAD occlusion followed by 180 min of reperfusion (n = 15). Histochemical staining (TTC) was performed in hearts from 5 additional cats subjected to 40 min of LAD occlusion and 180 min of reperfusion. Regional function was measured by sonomicrometry in the circumferential (CIRC) and longitudinal (LONG) axis of the anterior left ventricular midwall. Myocardial blood flow was measured with radiolabelled microspheres. Adenine nucleotides in the subepi- and subendocardium were measured with high-pressure liquid chromatography after LAD occlusion and after reperfusion.Ten minutes of ischaemia induced a transmurally uniform ATP depletion. Repletion of ATP following reperfusion was transmurally uniform. Recovery of regional shortening was non-uniform with better recovery in CIRC (76 +/- 8% vs. LONG; 46 +/- 10%, P < 0.05). Forty minutes of ischaemia induced a more severe ATP depletion in the subendocardium compared to the subepicardium. A slight recovery of ATP following reperfusion was transmurally uniform. Recovery of function was present only in CIRC (48 +/- 6%). Tissue blood flow showed a transmurally homogenous flow restriction during ischaemia and uniform recovery following reperfusion. TTC staining demonstrated predominantly subendocardial infarctions following 40 min of regional ischaemia.Postischaemic recovery of regional function is non-uniform and independent of ATP repletion and collateral blood flow during ischaemia. Absence of functional recovery in LONG is associated with development of infarction.
Lung Adenocarcinoma Global Profiling Identifies Type II Transforming Growth Factor-β Receptor as a Repressor of Invasiveness
Authors: Alain C. Borczuk, Han K. Kim, Hilary A. Yegen, Richard A. Friedman, Charles A. Powell
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Lung adenocarcinoma histology and clinical outcome are heterogeneous and associated with tumor invasiveness.We hypothesized that invasiveness is associated with a distinct molecular signature and that genes differentially expressed in tumor or adjacent stroma will identify cell surface signal transduction and matrix remodeling pathways associated with the acquisition of invasiveness in lung adenocarcinoma.Microarray analysis of microdissected noninvasive bronchioloalveolar carcinoma (BAC) and invasive adenocarcinoma and adenocarcinoma-mixed type with BAC features identified transcriptional profiles of lung adenocarcinoma invasiveness. Among the signature set that was lower in adenocarcinoma-mixed compared with BAC was the type II transforming growth factor beta (TGF-beta) receptor, suggesting downregulation of TGFbetaRII is an early event in lung adenocarcinoma metastasis. Immunostaining in independently acquired specimens demonstrated a correlation between TbetaRII expression and length of tumor invasion. Repression of TGFbetaRII in lung cancer cells increased tumor cell invasiveness and activated p38 mitogen-activated protein kinases. Microarray analysis of invasive cells identified potential downstream mediators of TGFbetaRII with differential expression in lung adenocarcinomas.The repression of type II TGF-beta receptor may act as a significant determinant of lung adenocarcinoma invasiveness, an early step in tumor progression toward metastasis.
Quantitative evaluation of the improvement in the pharmacokinetics of a nucleic acid drug delivery system by dynamic PET imaging with 18F-incorporated oligodeoxynucleotides
Authors: Hidefumi Mukai, Daiki Ozaki, Yilong Cui, Takeshi Kuboyama, Hiroko Yamato-Nagata, Kayo Onoe, Maiko Takahashi, Yasuhiro Wada, Takeshi Imanishi, Tetsuya Kodama, Satoshi Obika, Masaaki Suzuki, Hisashi Doi, Yasuyoshi Watanabe
Journal: Journal of Controlled Release (2014)
Only 5% of British people have made advance care plans, survey finds
Authors: G. Iacobucci
Journal: BMJ (2013)

Most people in Great Britain have not discussed or made any plans for when they die, increasing the likelihood that they will receive inappropriate care at the end of life, a new study has found.

The survey for the Dying Matters Coalition found that most people were leaving it too late to make their wishes known with regard to their end of life care. This created difficulties for families in making suitable arrangements and made it harder for them to cope with bereavement, the coalition said.

This is despite the fact that almost two thirds (63%) of respondents said …
Systemic Anaphylaxis in the Human Being
Authors: K. Frank Austen
Journal: New England Journal of Medicine (1974)

THE term "anaphylaxis" was introduced by Poitier and Richet1 to describe the profound shock with subsequent death produced in some dogs upon reinjection of the poison of the sea anemone. The occurrence of a fatal response to repeat injection rather than a demonstration of immunity or prophylaxis to the foreign protein prompted the designation anaphylaxis. The clinical manifestations of the anaphylactic syndrome are entirely due to the action of diverse chemical mediators released with great rapidity by antigen activation of a discrete number of target cells previously sensitized by interaction with antibody; the chemical mediators — histamine, slow reacting substance . . .
Combined pulmonary and thoracic wall resection for stage III lung cancer.
Authors: S S Shah, P Goldstraw
Journal: Thorax (1995)

Carcinoma of the lung with thoracic wall involvement constitutes stage III disease. The management of patients with this condition is complicated. However, improvement in perioperative care coupled with advances in surgical technique have enabled a more aggressive approach to the problem to be adopted.A retrospective review was carried out of 58 patients (40 men) of mean age 63 years who underwent thoracotomy for lung cancer with chest wall invasion between 1980 and 1993.Chest wall resection was performed in 55 patients (94.8%); in three patients the discovery of N2 disease at operation precluded resection. The TNM status was T3N0M0 in 38 patients, T3N1M0 in 13, and T3N2M0 in seven. Squamous cell carcinoma was the commonest cell type (26 patients). Reconstruction of the chest wall was performed in 29 patients (Marlex mesh in six, Marlex-methacrylate in 22, myocutaneous flap in one patient). The morbidity and mortality were 22.4% and 3.4% respectively. Follow up was complete in 51 patients. Nineteen (37.2%) survived > or = 5 years. The absolute five year survival for N0 and N1 disease was 44.7% and 38.4%, respectively. No patients with N2 disease survived five years.In patients with carcinoma of the lung and chest wall invasion, combined pulmonary and thoracic wall resection offers the prospect of cure with minimal morbidity and mortality. The prognosis of patients with coexistent N2 disease remains poor.
Cellular and molecular mechanisms of sex differences in renal ischemia–reperfusion injury
Authors: A KHER, K MELDRUM, M WANG, B TSAI, J PITCHER, D MELDRUM
Journal: Cardiovascular Research (2005)

Renal ischemia–reperfusion (I/R) is an important etiopathological mechanism of acute renal failure (ARF). Despite improvements in the treatment of ARF, it is associated with significant morbidity and mortality. I/R injury also occurs during renal transplantation and leads to reduced allograft survival. Sex differences have been found in I/R injury in many different organs including the kidney. Women have half the mortality of men in ARF. In animal models also, females are protected against renal I/R injury. The mechanisms by which sex affects the outcome to renal I/R injury are being actively investigated. This review will examine the evidence for gender differences in renal I/R injury and discuss the probable mechanisms by which sex affects the renal response to I/R injury.
Resistance Training To Counteract the Catabolism of a Low-Protein Diet in Patients with Chronic Renal Insufficiency
Authors: Carmen Castaneda, Patricia L. Gordon, Katherine Leigh Uhlin, Andrew S. Levey, Joseph J. Kehayias, Johanna T. Dwyer, Roger A. Fielding, Ronenn Roubenoff, Maria Fiatarone Singh
Journal: Annals of Internal Medicine (2001)

Background: Chronic renal insufficiency leads to muscle wasting, which may be exacerbated by low-protein diets prescribed to delay disease progression. Resistance training increases protein utilization and muscle mass. Objective: To determine the efficacy of resistance training in improving protein utilization and muscle mass in patients with chronic renal insufficiency treated with a low-protein diet. Design: Randomized, controlled trial. Setting: Tufts University, Boston, Massachusetts. Patients: 26 older patients with moderate renal insufficiency (17 men, 9 women) who had achieved stabilization on a low-protein diet. Intervention: During a run-in period of 2 to 8 weeks, patients were instructed and their adherence to the low-protein diet (0.6 g/kg of body weight per day) was evaluated. They were randomly assigned to a low-protein diet plus resistance training (n = 14) or a low-protein diet alone (n = 12) for 12 weeks. Measurements: Total body potassium, mid-thigh muscle area, type I and II muscle-fiber cross-sectional area, and protein turnover. Results: Mean protein intake was 0.64 ± 0.07 g/kg per day after stabilization. Total body potassium and type I and II muscle-fiber cross-sectional areas increased in patients who performed resistance training by a mean (±SD) of 4% ± 8%, 24% ± 31%, and 22% ± 29%, respectively, compared with those who did not. Leucine oxidation and serum prealbumin levels also improved significantly. Patients assigned to resistance training maintained body weight compared with those who were not. Improvement in muscle strength was significantly greater with resistance training (32% ± 14%) than without (−13% ± 20%) (P < 0.001). Conclusion: By improving muscle mass, nutritional status, and function, resistance training seems to be effective against the catabolism of a low-protein diet and uremia in patients with renal failure.