tbuckley/cabot-search huggingface dataset:
Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on gas exchange and haemodynamics
Authors: D. Walmrath, F. Grimminger, D. Pappert, C. Knothe, U. Obertacke, A. Benzing, A. Günther, T. Schmehl, H. Leuchte, W. Seeger
Journal: European Respiratory Journal (2002)

The aim of the present study was to investigate the feasibility and efficacy of bronchoscopic surfactant administration in a noncontrolled multicentre study in five university centres. A total number of 27 patients, suffering from severe acute respiratory distress syndrome (mean±sem lung injury score: 3.15±0.06) and septic shock (Acute Physiology and Chronic Health Evaluation (APACHE) II score at study entry 33.2±1.3, lactate 4.3±0.6 mmol·L −1 ) were studied. The patients were ventilated with a mean tidal volume of 11.0±0.5 mL·kg −1 body weight (bw), either volume or pressure controlled, with 16.3±2.8 cmH 2 O positive end-expiratory pressure, for an average of 3.5±0.3 days at study entry. A natural bovine surfactant extract (300 mg·kg −1 bw Alveofact®; mean total volume 378 mL) was delivered in divided doses to each segment of the lungs via flexible bronchoscope within ∼45 min. No untoward effects on gas exchange, lung mechanics and haemodynamics were noted during the procedure of surfactant administration. Within 12 h the oxygen tension in arterial blood/inspiratory oxygen fraction increased from a mean of 109±8 mmHg to 210±20 mmHg (p&lt;0.001). In seven patients, in whom gas exchange again deteriorated with further progression of the disease, a second surfactant dose of 200 mg·kg −1 was administered 18–24 h after the first application, again improving arterial oxygenation. A total of 15 patients survived the 28-day study period (mortality rate 44.4%, compared to a calculated risk of death for the given APACHE II scores of 74.0±3.5%), with all causes of death being nonrespiratory. The bronchoscopic application of a high dose of natural surfactant in patients with severe acute respiratory distress syndrome and septic shock is both feasible and safe, resulting in a pronounced improvement in gas exchange.
Smoking Termination Opportunity for inPatients (STOP): superiority of a course of varenicline tartrate plus counselling over counselling alone for smoking cessation: a 12-month randomised controlled trial for inpatients
Authors: Brian James Smith, Kristin Veronica Carson, Malcolm Philip Brinn, Nadina Ann Labiszewski, Matthew J Peters, Robert Fitridge, Simon A Koblar, Jim Jannes, Antony J Veale, Sharon J Goldsworthy, John Litt, David Edwards, Adrian Jeffrey Esterman
Journal: Thorax (2012)

<h3>Rationale</h3> Smoking cessation interventions in outpatient settings have been demonstrated to be cost effective. Given this evidence, we aimed to evaluate the effectiveness of varenicline tartrate plus Quitline-counselling compared with Quitline-counselling alone when initiated in the <i>inpatient</i> setting. <h3>Methods</h3> Adult patients (18–75 years) admitted with a smoking-related illness to three hospitals, were randomised to receive either 12-weeks of varenicline tartrate plus Quitline-counselling, (n=196) or Quitline-counselling alone, (n=196), with 12-months follow-up. <h3>Results</h3> For the primary analysis population (intention-to-treat), the proportion of subjects who remained continuously abstinent were significantly greater in the varenicline plus counselling arm (31.1%, n=61) compared with counselling alone (21.4%, n=42; RR 1.45, 95% CI 1.03 to 2.03, p=0.03). <h3>Conclusions</h3> The combined use of varenicline plus counselling when initiated in the inpatient setting has produced a sustained smoking cessation benefit at 12-months follow-up, indicating a successful opportunistic treatment for smokers admitted with smoking related illnesses. <h3>Trial registration</h3> http://www.clinicaltrials.gov/ ClinicalTrials.gov identification number: NCT01141855.
Combined Allogeneic Tumor Cell Vaccination and Systemic Interleukin 12 Prevents Mammary Carcinogenesis in HER-2/neu Transgenic Mice
Authors: Patrizia Nanni, Giordano Nicoletti, Carla De Giovanni, Lorena Landuzzi, Emma Di Carlo, Federica Cavallo, Serenella M. Pupa, Ilaria Rossi, Mario P. Colombo, Cinzia Ricci, Annalisa Astolfi, Piero Musiani, Guido Forni, Pier-Luigi Lollini
Journal: The Journal of Experimental Medicine (2001)

Transgenic Balb/c mice expressing the transforming rat HER-2/neu oncogene develop early and multifocal mammary carcinomas. Within the first 5 months of life the tissue-specific expression of HER-2/neu causes a progression in all their 10 mammary glands from atypical hyperplasia to invasive carcinoma. It was previously observed that chronic administration of interleukin (IL)-12 increased tumor latency, but every mouse eventually succumbed to multiple carcinomas. A significant improvement in tumor prevention was sought by administering allogeneic mammary carcinoma cells expressing HER-2/neu combined with systemic IL-12. This treatment reduced tumor incidence by 90% and more than doubled mouse lifetime. For the maximum prevention p185neu antigen must be expressed by allogeneic cells. IL-12 treatment strongly increased the cell vaccine efficacy. The mammary glands of mice receiving the combined treatment displayed a markedly reduced epithelial cell proliferation, angiogenesis, and HER-2/neu expression, while the few hyperplastic foci were heavily infiltrated by granulocytes, macrophages, and CD8+ lymphocytes. Specific anti–HER-2/neu antibodies were produced and a nonpolarized activation of CD4+ and CD8+ cells secreting IL-4 and interferon (IFN)-γ were evident. A central role for IFN-γ in the preventive effect was proven by the lack of efficacy of vaccination in IFN-γ gene knockout HER-2/neu transgenic Balb/c mice. A possible requirement for IFN-γ is related to its effect on antibody production, in particular on IgG2a and IgG2b subclasses, that were not induced in IFN-γ knockout HER-2/neu mice. In conclusion, our data show that an allogeneic HER-2/neu–expressing cell vaccine combined with IL-12 systemic treatment can prevent the onset of genetically determined tumors.
Analysis of MHC class II DP, DQ and DR alleles in Crohn’s disease
Authors: A Cariappa, B Sands, D Forcione, D Finkelstein, D K Podolsky, S Pillai
Journal: Gut (1998)

Although inflammation in Crohn's disease is believed to be mediated by activated T cells, genotyping of all MHC class II alleles in white people with this disease has not been reported.To perform a detailed molecular analysis of HLA DPB, DQB, and DRB genes in white patients with Crohn's disease and controls in order to determine if the inheritance of any class II genes confers susceptibility or resistance to this disease.Complete molecular typing of HLA class II DPB, DQB, and DRB alleles was performed in 58 white patients with Crohn's disease and 93 healthy controls using a polymerase chain reaction-sequence specific oligonucleotide based approach.No significant association with any DPB or DQB alleles was noted in patients with Crohn's disease. Since our previous studies had shown a strong association of an HLA DRB3*0301/DRB1*1302 haplotype with Crohn's disease, we re-examined this association using more stringent genotyping criteria. This haplotype was present in 20.7% of patients and 5.4% of controls (p = 0.0066; relative risk = 4.59).The DRB3*0301/DRB1*1302 haplotype is the only significant MHC class II association noted in white people with Crohn's disease and represents the strongest association of any MHC or non-MHC locus with this disease.
THE ACTIN CYTOSKELETON: Integrating Form and Function at the Synapse
Authors: Christian Dillon, Yukiko Goda
Journal: Annual Review of Neuroscience (2005)

Synapses are highly specialized intercellular junctions that mediate the transmission of information between axons and target cells. A fundamental property of synapses is their ability to modify the efficacy of synaptic communication through various forms of synaptic plasticity. Recent developments in imaging techniques have revealed that synapses exhibit a high degree of morphological plasticity under basal conditions and also in response to neuronal activity that induces alterations in synaptic strength. The underlying molecular basis for this morphological plasticity has attracted much attention, yet its functional significance to the mechanisms of synaptic transmission and synaptic plasticity remains elusive. These morphological changes ultimately require the dynamic actin cytoskeleton, which is the major structural component of synapses. Delineating the physiological roles of the actin cytoskeleton in supporting synaptic transmission and synaptic plasticity, therefore, paves the way for gaining molecular insights into when and how synaptic machineries couple synapse form and function.
Prospective Multicenter Validation of the Independent Prognostic Value of the Mitotic Activity Index in Lymph Node–Negative Breast Cancer Patients Younger Than 55 Years
Authors: Jan P.A. Baak, Paul J. van Diest, Feja J. Voorhorst, Elsken van der Wall, Louk V.A.M. Beex, Jan B. Vermorken, Emiel A.M. Janssen
Journal: Journal of Clinical Oncology (2005)

Purpose To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN) –negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study. Patients and Methods Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies. Results Distant metastases occurred in 127 patients (24.6%); 90 (17.4%) died as a result of metastases. MAI (&lt; 10, ≥ 10) showed strong association with recurrence (hazard ratio [HR], 3.12; 95% CI, 2.17 to 4.50; P ≤ .0001) and mortality (HR, 4.42; 95% CI, 2.79 to 7.01; P &lt; .0001). The absolute difference in 10-year Kaplan-Meier estimates of time to distant recurrence as well as survival was 22% between MAI less than 10 versus ≥ 10. This effect was independent of age, estrogen receptor (ER) status, and tumor diameter (which were significant prognosticators). In multivariate analysis with regard to patient age, tumor diameter, grade, ER status, and the St Gallen criterion, MAI proved to be an independent and the strongest prognosticator. Tubular formation (TF) and nuclear atypia (NA), as constituents of (expert revised) grade, had no (for TF) or limited (for NA, P = .048) additional prognostic value to the MAI. In the group with MAI less than 10, MAI less than 3 versus more than 3 had additional value but the classical threshold of 0 to 5 v 6 to 10 did not. With this additional subdivision of MAI as less than 3, 3 to 9, and more than 9, NA lost its additive prognostic value. Conclusion The MAI is the strongest, most widely available, easily assessable, inexpensive, well-reproducible prognosticator and is well suited to routinely differentiate between high- and low-risk LN-negative breast cancer patients younger than 55 years.
Noninvasive Monitoring of Serial Changes in Pulmonary Vascular Resistance and Acute Vasodilator Testing Using Cardiac Magnetic Resonance
Authors: Ana García-Álvarez, Leticia Fernández-Friera, José Manuel García-Ruiz, Mario Nuño-Ayala, Daniel Pereda, Rodrigo Fernández-Jiménez, Gabriela Guzmán, Damián Sanchez-Quintana, Angel Alberich-Bayarri, David Pastor-Escuredo, David Sanz-Rosa, Jaime García-Prieto, Jesús G. Gonzalez-Mirelis, Gonzalo Pizarro, Luis Jesús Jimenez-Borreguero, Valentín Fuster, Javier Sanz, Borja Ibáñez
Journal: Journal of the American College of Cardiology (2013)
Bacterial-induced release of inflammatory mediators by bronchial epithelial cells
Authors: OA Khair, RJ Davies, JL Devalia
Journal: European Respiratory Journal (1996)

This review focuses on bacterial induction and release of inflammatory cytokines and adhesion molecules by human bronchial epithelial cells, with special reference to Haemophilus influenzae, a pathogen commonly associated with chronic bronchitis. Studies investigating the mechanisms underlying bacterial colonization of the airways and bacterial-induced chronic airway inflammation have suggested that these are likely to involve localization of bacteria to the site(s) of infection in the respiratory tract and induction of a local airway inflammation resulting in the initiation of epithelial damage. We have hypothesized that the gross airway epithelial damage observed in chronic infective lung disease is an indirect consequence of proteolytic enzymes and toxic oxygen radicals generated by large numbers of neutrophils infiltrating the airways. Furthermore, the infiltration and activation of the neutrophils is a consequence of increased release of proinflammatory mediators from the host respiratory epithelium, induced by bacterial products, such as endotoxin. This hypothesis is based on studies which have demonstrated that the concentrations of circulating cytokines, such as interleukin (IL)-8 and tumour necrosis factor-alpha (TNF-alpha), which have profound effects on neutrophil activity, are increased in endotoxaemia and that airway epithelial cells are a rich source of these cytokines. Support for this hypothesis is provided by studies of cultured human bronchial epithelial cells incubated either in the absence or presence of purified endotoxin preparations from nontypable and type b H. influenzae strains which have demonstrated that these endotoxins lead to significantly increased expression and/or release of proinflammatory mediators, including IL-6, IL-8, TNF-alpha and intercellular adhesion molecule-1 (ICAM-1). Treatment of the cells with steroids can downregulate the expression and/or release of these inflammatory mediators. Additionally, these studies have demonstrated that culture medium collected from endotoxin-treated cultures, 24 h after treatment, significantly increases neutrophil chemotaxis and adhesion to human endothelial cells in vitro.
Peritoneal Dialysis In Quinine Intoxication
Authors: James V. Donadio
Journal: JAMA (1968)

To the Editor:—  Our experience with removal of quinine by peritoneal dialysis and mannitol-enhanced urinary excretion of quinine is remarkably different from the observations of Markham et al (202:1102, 1967). Removal of quinine by peritoneal dialysis (Table 1) compares our four patients withPlasmodium falciparummalaria complicated by acute renal failure with Markham's patient.  Even at plasma quinine concentrations which were generally higher than in Markham's patient, the total removal of quinine and removal rate of quinine by peritoneal dialysis in our patients was trivial. In 56 peritoneal-clearance periods, quinine clearance was remarkably low, varying from 1 ml to 8 ml/min. Peritoneal clearances (C=UV)/P were calculated with total outflow volume (V), aliquots of each pooled outflow volume for quinine determinations (U), and mid-clearance blood samples (P). Clearance periods, which were timed from commencement of inflow to completion of outflow, were approximately 60 minutes in duration. The poor peritoneal clearance
Nonrandom divergence of gene expression following gene and genome duplications in the flowering plant Arabidopsis thaliana.
Authors: Tineke Casneuf, Stefanie De Bodt, Jeroen Raes, Steven Maere, Yves Van de Peer
Journal: Genome biology (2006)

Genome analyses have revealed that gene duplication in plants is rampant. Furthermore, many of the duplicated genes seem to have been created through ancient genome-wide duplication events. Recently, we have shown that gene loss is strikingly different for large- and small-scale duplication events and highly biased towards the functional class to which a gene belongs. Here, we study the expression divergence of genes that were created during large- and small-scale gene duplication events by means of microarray data and investigate both the influence of the origin (mode of duplication) and the function of the duplicated genes on expression divergence. Duplicates that have been created by large-scale duplication events and that can still be found in duplicated segments have expression patterns that are more correlated than those that were created by small-scale duplications or those that no longer lie in duplicated segments. Moreover, the former tend to have highly redundant or overlapping expression patterns and are mostly expressed in the same tissues, while the latter show asymmetric divergence. In addition, a strong bias in divergence of gene expression was observed towards gene function and the biological process genes are involved in. By using microarray expression data for Arabidopsis thaliana, we show that the mode of duplication, the function of the genes involved, and the time since duplication play important roles in the divergence of gene expression and, therefore, in the functional divergence of genes after duplication.
Clinically Identified Maternal Depression Before, During, and After Pregnancies Ending in Live Births
Authors: Patricia M. Dietz, Selvi B. Williams, William M. Callaghan, Donald J. Bachman, Evelyn P. Whitlock, Mark C. Hornbrook
Journal: American Journal of Psychiatry (2007)

This study estimated the prevalence of diagnosed depression and treatment among women before, during, and after pregnancies ending in live births.A previously validated algorithm identified health plan members with at least one pregnancy between Jan. 1, 1998, and Dec. 31, 2001. Women with a pregnancy ending in one or more live births and continuously enrolled from 39 weeks before pregnancy through 39 weeks after pregnancy were eligible. Maternal depression was identified from the medical records. Depression treatment included antidepressant medication and/or mental health visits. The authors examined the prevalence of depression and treatments received.Among 4,398 continuously enrolled women with eligible pregnancies ending in live births, 678 (15.4%) had depression identified during at least one pregnancy phase; 8.7%, 6.9%, and 10.4% had depression identified before, during, and/or after pregnancy, respectively. Among women with identified depression during the 39 weeks before pregnancy, 56.4% also had a depression diagnosis during pregnancy. Of women identified with depression during the 39 weeks following pregnancy, 54.2% had depression diagnoses either during or preceding pregnancy. Most women diagnosed with depression received antidepressant medications and/or had at least one mental health visit. Having at least one mental health visit did not vary before, during, or after pregnancy; however, antidepressant use was lower during pregnancy than before or after pregnancy.Approximately one in seven women was identified with and treated for depression during 39 weeks before through 39 weeks after pregnancy, and more than half of these women had recurring indicators for depression.
CELLULAR DIFFERENTIATION IN THE THYMUS
Authors: D. G. Colley, A. Y. Shih Wu, B. H. Waksman
Journal: The Journal of Experimental Medicine (1970)

Young adult rat thymus and lymph node cell subpopulations were obtained by differential flotation on discontinuous BSA density gradients and assayed for properties characteristic of mature thymus-derived lymphocytes. One such subpopulation (C) of thymocytes was enriched in its ability to respond mitotically to a hemiallogeneic MLR stimulus, to localize in the parenchyma of lymph nodes and spleen, and to initiate a GVH reaction in a suitable host. These cells did not respond well to mitotic stimulation by PHA, they were lighter in density than the majority of mature lymph node thymus-derived lymphocytes, and they possessed a thymus-specific antigen (RTA) not present on peripheral lymphoid cells. We conclude that the acquisition of peripheral properties occurs sequentially, during an intrathymic differentiation cycle or shortly after the cells leave the thymus.
Effect of vasopressin on electrical potential difference and chloride transport in mouse medullary thick ascending limb of Henle's loop.
Authors: D A Hall, D M Varney
Journal: Journal of Clinical Investigation (1980)

Medullary thick ascending limbs of Henle's loop of the Swiss-Webster mouse were perfused in vitro with an isotonic perfusate and a Ringer's bathing medium. In five studies, addition of a supramaximal concentration of synthetic arginine vasopressin (AVP) to the bathing medium resulted in an increase in electrical potential difference (PD) from 5.0 +/- 1.5 mV, lumen positive, to 10.7 +/- 1.4 mV (P < 0.001). When AVP was removed, the PD returned to 2.6 +/- 0.9 mV (P < 0.001), then increased again to 6.9 +/- 1.7 mV (P < 0.01) when AVP was added a second time. A significant, but submaximal, increase in PD of 2.3 +/- 0.6 MV (P < 0.05) was observed in five medullary thick ascending limbs when AVP was added to the bathing medium at a concentration of 10 microunits/ml. This increase was approximately one-third of the response observed at a concentration of 100 microunits/ml in the same tubule. No further increment in PD was observed in five medullary thick ascending limbs when the AVP concentration was increased from 100 to 1,000 microunits/ml. In seven thick ascendcing limbs, the effect of AVP on PD was reproduced by the addition of 8-[p-chlorophenylthio]-cyclic 3',5'-adenosine monophosphate to the bathing medium at a final concentration of 0.1 mM. AVP increased unidirectional chloride flux from lumen to bath from 29.3 +/- 3.2 to 69.8 +/- 6.2 peq/cm per s (P < 0.001) in spite of an increase in the lumen positive PD from 1.6 +/- 0.5 mV to 7.0 +/- 0.6 mV (P < 0.001). Unidirectional chloride flux from bath to lumen was not affected by AVP. In another series of experiments, net chloride flux increased from 15.6 +/- 3.0 to 41.7 +/- 5.3 peq/cm per s (P < 0.05) after addition of AVP. The effect of AVP on hydraulic water permeability (Lp) was examined by adding raffinose to the bathing medium in both the presence and the absence of AVP. The calculated Lp of 16 +/- 2 nm/s per atm in the absence of AVP, although very low, was significantly different from zero (P < 0.01). However, the Lp did not increase significantly when AVP was added to the bathing medium. These results suggest that AVP has a second site of action in the kidney to increase chloride transport by the medullary thick ascending limb in addition to its well-known effect on the water permeability of the collecting tubule. The former effect would contribute to urinary concentrating ability by increasing the axial osmotic gradient in the renal medulla.
Heart disease prevention should not be left to professionals
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

Information to prevent heart disease must be taken to workplaces, schools, and religious institutions, not left to health professionals, says a new guideline from the American Heart Association.

The guideline complements the national action plan for cardiovascular health, to be issued by the Centers for Disease Control and Prevention in April ( Circulation 2003;107:645-51 and http://www.circulationaha.org/).

“Heart disease kills half the people in a community,” said lead author Dr Thomas Pearson, chairman of the Department of Community and Preventive Medicine at the …