tbuckley/cabot-search huggingface dataset:
The development and validation of the King's Brief Interstitial Lung Disease (K-BILD) health status questionnaire
Authors: Amit S Patel, Richard J Siegert, Katherine Brignall, Patrick Gordon, Sophia Steer, Sujal R Desai, Toby M Maher, Elisabetta A Renzoni, Athol U Wells, Irene J Higginson, Surinder S Birring
Journal: Thorax (2012)

Health status is impaired in patients with interstitial lung disease (ILD). There is a paucity of tools that assess health status in ILD. The objective of this study was to develop and validate the King's Brief Interstitial Lung Disease questionnaire (K-BILD), a new health status measure for patients with ILD.Patients with ILD were recruited from outpatient clinics. The development of the questionnaire consisted of three phases: item generation; item reduction, allocation to domains by factor analysis, Rasch analysis to create unidimensional scales and validation; and repeatability testing.173 patients with ILD (49 with idiopathic pulmonary fibrosis) completed a preliminary 71-item questionnaire. 56 items were removed due to redundancy, low factor loadings or poor fit to the Rasch model. The final version of the K-BILD questionnaire consisted of 15 items and three domains (breathlessness and activities, chest symptoms and psychological). Internal consistency assessed with Cronbach's α coefficient was 0.94 for the K-BILD total score. Concurrent validity of the K-BILD questionnaire was high compared with St George's Respiratory Questionnaire (r=0.90) and moderate with lung function (vital capacity, r=0.50). The K-BILD questionnaire was repeatable over 2 weeks (n=44), with intraclass correlation coefficients for domains and total score 0.86-0.94. The K-BILD construct validity for patients with idiopathic pulmonary fibrosis was similar to that of other ILDs.The K-BILD questionnaire is a brief, valid, self-completed health status measure for ILD. It could be used in the clinic to assess ILD from the patients' perspective.
Childhood Obesity, Other Cardiovascular Risk Factors, and Premature Death
Authors: Paul W. Franks, Robert L. Hanson, William C. Knowler, Maurice L. Sievers, Peter H. Bennett, Helen C. Looker
Journal: New England Journal of Medicine (2010)

The effect of childhood risk factors for cardiovascular disease on adult mortality is poorly understood.In a cohort of 4857 American Indian children without diabetes (mean age, 11.3 years; 12,659 examinations) who were born between 1945 and 1984, we assessed whether body-mass index (BMI), glucose tolerance, and blood pressure and cholesterol levels predicted premature death. Risk factors were standardized according to sex and age. Proportional-hazards models were used to assess whether each risk factor was associated with time to death occurring before 55 years of age. Models were adjusted for baseline age, sex, birth cohort, and Pima or Tohono O'odham Indian heritage.There were 166 deaths from endogenous causes (3.4% of the cohort) during a median follow-up period of 23.9 years. Rates of death from endogenous causes among children in the highest quartile of BMI were more than double those among children in the lowest BMI quartile (incidence-rate ratio, 2.30; 95% confidence interval [CI], 1.46 to 3.62). Rates of death from endogenous causes among children in the highest quartile of glucose intolerance were 73% higher than those among children in the lowest quartile (incidence-rate ratio, 1.73; 95% CI, 1.09 to 2.74). No significant associations were seen between rates of death from endogenous or external causes and childhood cholesterol levels or systolic or diastolic blood-pressure levels on a continuous scale, although childhood hypertension was significantly associated with premature death from endogenous causes (incidence-rate ratio, 1.57; 95% CI, 1.10 to 2.24).Obesity, glucose intolerance, and hypertension in childhood were strongly associated with increased rates of premature death from endogenous causes in this population. In contrast, childhood hypercholesterolemia was not a major predictor of premature death from endogenous causes.
Intracellular activation of trypsinogen in transgenic mice induces acute but not chronic pancreatitis
Authors: S. Gaiser, J. Daniluk, Y. Liu, L. Tsou, J. Chu, W. Lee, D. S. Longnecker, C. D. Logsdon, B. Ji
Journal: Gut (2011)

Background and aims Premature intra-acinar activation of trypsinogen is widely considered key for both the initiation of acute pancreatitis and the development of chronic pancreatitis. However, the biological consequences of intracellular trypsinogen activation have not been directly examined. To do so, a new mouse model was developed. Methods Mice were engineered to conditionally express an endogenously activated trypsinogen within pancreatic acinar cells (PACE-trypon). Hallmarks of pancreatitis were determined and findings were correlated to the level (zygosity) and extent (temporal and spatial) of conditional PACE-trypon expression. Furthermore, the impact of acinar cell death in PACE-trypon mice was assessed and compared with a model of selective diphtheria toxin (DT)-mediated induction of acinar apoptosis. Results Initiation of acute pancreatitis was observed with high (homozygous), but not low (heterozygous) levels of PACE-trypon expression. Subtotal (maximal-rapid induction) but not limited (gradual-repetitive induction) conditional PACE-trypon expression was associated with systemic complications and mortality. Rapid caspase-3 activation and apoptosis with delayed necrosis was observed, and loss of acinar cells led to replacement with fatty tissue. Chronic inflammation or fibrosis did not develop. Selective depletion of pancreatic acinar cells by apoptosis using DT evoked similar consequences. Conclusions Intra-acinar activation of trypsinogen is sufficient to initiate acute pancreatitis. However, the primary response to intracellular trypsin activity is rapid induction of acinar cell death via apoptosis which facilitates resolution of the acute inflammation rather than causing chronic pancreatitis. This novel model provides a powerful tool to improve our understanding of basic mechanisms occurring during pancreatitis.
Hepatic Prolactin Binding in Female Sprague-Dawley Rats Fed a Diet High in Corn Oil23
Authors: William C. Wetsel, Adrianne E. Rogers
Journal: JNCI Journal of the National Cancer Institute (1984)

The relationship between dietary fat content and hepatic prolactin (PRL) binding during the four stages of the estrous cycle was examined. Serum 17β-estradiol, PRL, and progesterone were also monitored in the same animals. Female SD rats were fed 5 or 24% corn oil in nutritionally balanced diets, given 2.5 mg 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6] or vehicle by gavage at 8 weeks of age, and decapitated at noon on 1 of the 4 days of the estrous cycle 2–5 weeks later. Analysis of hepatic PRL binding data by Scatchard plots revealed no effect of diet or DMBA. PRL binding was lowest at proestrus, increased at estrus, remained elevated at metestrus, and declined at diestrus. Diet also had no effect on serum hormone concentrations, which showed the expected pattern during the estrous cycle in all treatment groups. Results reported by others of an effect of dietary corn oil content on hepatic PRL binding may have been due to use of control diets low in essential fatty acids.
Adverse effects of maternal smoking during pregnancy on innate immunity in infants
Authors: P. N. Le Souef
Journal: European Respiratory Journal (2006)

The potentially fatal effects of maternal smoking on infants have been recognised since the 1800s 1. In the latter half of the 1900s, the link between maternal smoking and the increased rate of lower respiratory infection (LRI) in early life was described 2. Given the high rates of smoking in many societies 3, the burden of the increase in LRI is substantial. In a meta-analysis of relationships between parental smoking and respiratory disease, Li et al. 4 calculated that the odds ratio (OR) for hospitalisation of LRI in infancy or early childhood for those exposed to parental environmental tobacco smoke (ETS) compared with those not exposed was 1.93 (95% confidence interval (CI) 1.66–2.25). The risk was age related, as the ORs of prevalence of serious LRI were 1.71 (95% CI 1.33–2.20) and 1.25 (95% CI 0.88–1.78) for children aged 0–2 and 3–6 yrs, respectively. Li et al. 4 concluded that the results of community and hospital studies were broadly consistent, and showed that the child of a parent who smokes is at approximately twice the risk of having a serious respiratory tract infection requiring hospitalisation in early life. Indeed, early respiratory infection is not only a major cause of morbidity in developed countries, but, in developing countries, respiratory infection is also the leading cause of death in children 5.

There have been a large number of studies showing the relationships between maternal smoking and impaired lung function and increases in respiratory symptoms in infants and young children. An effect of maternal smoking on neonatal lung function has been demonstrated in a study …
A phase I–II study of concomitant chemoradiotherapy with paclitaxel (one-hour infusion), 5-fluorouracil and hydroxyurea with granulocyte colony stimulating factor support for patients with poor prognosis head and neck cancer
Authors: B. Brockstein, D.J. Haraf, K. Stenson, L. Sulzen, M.E. Witt, R.W. Weichselbaum, E.E. Vokes
Journal: Annals of Oncology (2000)
Correlation of Visco-elastic Properties of Large Arteries with Microscopic Structure
Authors: JULIA T. APTER, MURRAY RABINOWITZ, DOROTHY H. CUMMINGS
Journal: Circulation Research (1966)

The media of 14 regions of the aorta and 3 regions of the pulmonary artery of dogs were subjected to a step-function circumferential stretch taking 20 msec to complete. The tension rose synchronously with the increase in circumference, then dropped exponentially to a reasonably steady state within 2 sec. A mathematical model, developed consistent with this stress-relaxation curve, showed how to use the tension curves to measure a viscous, a serieselastic, and a parallel-elastic constant unique for a given curve. These constants were compared with the microscopic structure of the same or similar segments; collagen was determined as hydroxyproline in a water soluble fraction, elastin as hydroxyproline in the residue and from the width and number of elastic lamellae, and muscle from the nitrogen content of a nonfibrous fraction, from cell counts and from contractility. The constituents varied widely and independently enough to permit correlating viscous and elastic constants with microscopic structure. The viscous and series-elastic constants were higher where muscle content was high, and increased markedly when the muscle was tonically contracted. The parallel-elastic constant was high when elastin was high and in the presence of contracted muscle, but seemed independent of collagen content, at the moderate tensions tested.
Identification of transcripts with enriched expression in the developing and adult pancreas
Authors: Brad G Hoffman, Bogard Zavaglia, Joy Witzsche, Teresa Ruiz de Algara, Mike Beach, Pamela A Hoodless, Steven JM Jones, Marco A Marra, Cheryl D Helgason
Journal: Genome biology (2008)

Abstract Background Despite recent advances, the transcriptional hierarchy driving pancreas organogenesis remains largely unknown, in part due to the paucity of comprehensive analyses. To address this deficit we generated ten SAGE libraries from the developing murine pancreas spanning Theiler stages 17-26, making use of available Pdx1 enhanced green fluorescent protein (EGFP) and Neurog3 EGFP reporter strains, as well as tissue from adult islets and ducts. Results We used a specificity metric to identify 2,536 tags with pancreas-enriched expression compared to 195 other mouse SAGE libraries. We subsequently grouped co-expressed transcripts with differential expression during pancreas development using K -means clustering. We validated the clusters first using quantitative real time PCR and then by analyzing the Theiler stage 22 pancreas in situ hybridization staining patterns of over 600 of the identified genes using the GenePaint database. These were then categorized into one of the five expression domains within the developing pancreas. Based on these results we identified a cascade of transcriptional regulators expressed in the endocrine pancreas lineage and, from this, we developed a predictive regulatory network describing beta-cell development. Conclusion Taken together, this work provides evidence that the SAGE libraries generated here are a valuable resource for continuing to elucidate the molecular mechanisms regulating pancreas development. Furthermore, our studies provide a comprehensive analysis of pancreas development, and insights into the regulatory networks driving this process are revealed.
Breast Cancer Cells Respond Differentially to Modulation of TGFβ2 Signaling after Exposure to Chemotherapy or Hypoxia
Authors: Siobhan K. O'Brien, Liang Chen, Wenyan Zhong, Douglas Armellino, Jiyang Yu, Christine Loreth, Maximillian Follettie, Marc Damelin
Journal: Cancer Research (2015)

Intratumoral heterogeneity helps drive the selection for diverse therapy-resistant cell populations. In this study, we demonstrate the coexistence of two therapy-resistant populations with distinct properties that are reproducibly enriched under conditions that characterize tumor pathophysiology. Breast cancer cells that survived chemotherapy or hypoxia were enriched for cells expressing the major hyaluronic acid receptor CD44. However, only CD44(hi) cells that survived chemotherapy exhibited cancer stem cell (CSC) phenotypes based on growth potential and gene expression signatures that represent oncogenic signaling and metastatic prowess. Strikingly, we identified TGFβ2 as a key growth promoter of CD44(hi) cells that survived chemotherapy but also as a growth inhibitor of cells that survived hypoxia. Expression of the TGFβ receptor TGFβR1 and its effector molecule SMAD4 was required for enrichment of CD44(hi) cells exposed to the chemotherapeutic drug epirubicin, which suggests a feed-forward loop to enrich for and enhance the function of surviving CSCs. Our results reveal context-dependent effects of TGFβ2 signaling in the same tumor at the same time. The emergence of distinct resistant tumor cell populations as a consequence of prior therapeutic intervention or microenvironmental cues has significant implications for the responsiveness of recurring tumors to therapy.
Non-psychogenic primary polydipsia in autoimmune chronic active hepatitis with severe hyperglobulinaemia.
Authors: M V Tobin, A I Morris
Journal: Gut (1988)

The association of hyperglobulinaemia with renal tubular acidosis and nephrogenic diabetes insipidus is well established. A patient with marked hyperglobulinaemia due to autoimmune chronic active hepatitis is described who presented with severe polydipsia and polyuria but had entirely normal renal tubular function indicating a primary thirst disorder.
Unusually High Incidence of Hepatitis B Virus Integration into the <i>MLL</i> Gene in Hepatocellular Carcinoma
Authors: Masahito Minami, Kota Fujiii, Masami Miyagawa, Takeshi Okanoue
Journal: Clinical Cancer Research (2006)

To the Editor: In their article, Tamori et al. ([1][1]) describe a common integration of hepatitis B virus (HBV) DNA into the MLL2 gene in 3 of 15 hepatocellular carcinomas (HCC). In all of the three cases of HBV integration into the MLL2 gene, they observed MLL2 RNA expression by reverse
Effects of ouabain and isoproterenol on left ventricular diastolic function during low-flow ischemia in isolated, blood-perfused rabbit hearts.
Authors: B H Lorell, S Isoyama, W N Grice, E O Weinberg, C S Apstein
Journal: Circulation Research (1988)

Myocardial ischemia causes both systolic and diastolic dysfunction. A variety of positive inotropic agents with different subcellular mechanisms may be used clinically in an attempt to reverse ischemic contractile failure. We tested the hypothesis that two inotropic agents, isoproterenol (a beta-adrenergic agonist) and ouabain (a sodium pump inhibitor), might have different effects on left ventricular (LV) diastolic function during ischemic failure despite an equivalent inotropic effect. Isolated isovolumic (balloon-in-LV) blood perfused rabbit hearts were paced at constant physiological heart rate (4 Hz), given either no drug (controls, n = 7), isoproterenol (n = 7), or ouabain (n = 7), and then subjected to 6 minutes of low flow ischemia (75% reduction of baseline coronary flow). The doses of isoproterenol and ouabain were selected to produce equivalent modest inotropic effects (15% increase in LV + dP/dt) in each heart during baseline perfusion conditions. During the ischemic period, there was a marked decrease in contractility, and neither isoproterenol nor ouabain demonstrated a positive inotropic effect relative to the control group. However, these agents had markedly different effects on diastolic chamber distensibility (assessed by end-diastolic pressure at constant LV volume) during ischemia. In the control and isoproterenol groups, diastolic chamber distensibility did not change during the ischemic period. In contrast, ouabain treatment resulted in a marked decrease in diastolic chamber distensibility during ischemia; this change was not completely reversible during the 10-minute reperfusion period. The mechanism by which ouabain decreased diastolic chamber distensibility relative to isoproterenol was assessed indirectly. The ouabain and isoproterenol groups were subjected to equivalent degrees of ischemia as assessed by oxygen supply/demand imbalance; during ischemia, each drug group did not differ with regard to myocardial perfusion rates, determinants of myocardial oxygen demand (heart rate, LV developed pressure, LV + dP/dt), myocardial oxygen consumption, lactate production, and ATP and creatine phosphate content. We therefore inferred that the greater decrease in diastolic distensibility in the ouabain group was not due to a greater metabolic severity of ischemia. These observations are consistent with a mechanism of cytosolic calcium overload induced by ouabain, resulting in persistent active myofilament tension development throughout diastole, to cause the observed decrease in diastolic chamber distensibility during ischemia in the ouabain group.(ABSTRACT TRUNCATED AT 400 WORDS)
A complaint that changed my practice
Authors: Antonio Munno
Journal: BMJ (2006)

The family asked to meet me. Their daughter had recovered from meningococcal septicaemia, and they wanted to know why I hadn't diagnosed it when they saw me that morning six weeks ago at the GP surgery. A few hours after I had treated her for an upper respiratory tract infection, her parents noticed a rash on her legs and took her straight to the accident and emergency department, where the seriousness of her condition was recognised.

The letter of complaint arrived a few weeks after she was discharged: How had I missed the …
Highly Biased CDR3 Usage in Restricted Sets of β Chain Variable Regions During Viral Superantigen 9 Response
Authors: Cristina Ciurli, David N. Posnett, Rafick-Pierre Sékaly, François Denis
Journal: The Journal of Experimental Medicine (1998)

Superantigens encoded by the mouse mammary tumor virus can stimulate a large proportion of T cells through interaction with germline-encoded regions of the T cell receptor β chain like the hypervariable region 4 (HV4) loop. However, several lines of evidence suggest that somatically generated determinants in the CDR3 region might influence superantigen responses. We stimulated T cells from donors differing at the BV6S7 allele with vSAG9 to assess the nature and structure of the T cell receptor in amplified T cells and to evaluate the contribution of non-HV4 elements in vSAG recognition. This report demonstrates that vSAG9 stimulation caused the expansion of TCR BV6-expressing T cells, although to varying degrees depending on the BV6 subfamily. The BV6S7 subfamily was preferentially expanded in all donors, but in donors homozygous for the BV6S7*2 allele, a significant number of BV6S5 T cells were amplified and showed a highly biased β chain junctional region (BJ) and CDR3 usage. As CDR3 regions are involved in major histocompatibility complex (MHC)–peptide interaction, such a selection is highly suggestive of an intimate MHC–TCR interaction and would imply that the topology of the MHC-vSAG-TCR complex is similar to the one occurring during conventional antigen recognition.
Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold
Authors: Per Fagerholm, Neil S. Lagali, Jeb A. Ong, Kimberley Merrett, W. Bruce Jackson, James W. Polarek, Erik J. Suuronen, Yuwen Liu, Isabelle Brunette, May Griffith
Journal: Biomaterials (2013)

We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation.
Suicide in HIV-Infected Individuals and the General Population in Switzerland, 1988–2008
Authors: Olivia Keiser, Adrian Spoerri, Martin W G Brinkhof, Barbara Hasse, Angéle Gayet-Ageron, Frédéric Tissot, Anna Christen, Manuel Battegay, Patrick Schmid, Enos Bernasconi, Matthias Egger
Journal: American Journal of Psychiatry (2009)

Objective High rates of suicide have been described in HIV-infected patients, but it is unclear to what extent the introduction of highly active antiretroviral therapy (HAART) has affected suicide rates. The authors examined time trends and predictors of suicide in the pre-HAART (1988–1995) and HAART (1996–2008) eras in HIV-infected patients and the general population in Switzerland. Method The authors analyzed data from the Swiss HIV Cohort Study and the Swiss National Cohort, a longitudinal study of mortality in the Swiss general population. The authors calculated standardized mortality ratios comparing HIV-infected patients with the general population and used Poisson regression to identify risk factors for suicide. Results From 1988 to 2008, 15,275 patients were followed in the Swiss HIV Cohort Study for a median duration of 4.7 years. Of these, 150 died by suicide (rate 158.4 per 100,000 person-years). In men, standardized mortality ratios declined from 13.7 (95% CI=11.0–17.0) in the pre-HAART era to 3.5 (95% CI=2.5–4.8) in the late HAART era. In women, ratios declined from 11.6 (95% CI=6.4–20.9) to 5.7 (95% CI=3.2–10.3). In both periods, suicide rates tended to be higher in older patients, in men, in injection drug users, and in patients with advanced clinical stage of HIV illness. An increase in CD4 cell counts was associated with a reduced risk of suicide. Conclusions Suicide rates decreased significantly with the introduction of HAART, but they remain above the rate observed in the general population, and risk factors for suicide remain similar. HIV-infected patients remain an important target group for suicide prevention.