tbuckley/cabot-search huggingface dataset:
Hyperinflation and respiratory muscle interaction
Authors: M Decramer
Journal: European Respiratory Journal (1997)

Hyperinflation clearly affects respiratory muscle interaction. It commonly increases the rib cage contribution to chest wall motion, whilst it reduces the abdominal contribution. This change is thought to result from the fact that hyperinflation severely reduces the mechanical advantage of the diaphragm, whilst it affects the mechanical advantage of the neck and rib cage muscles to a lesser extent. The mechanical disadvantage in the diaphragm induced by hyperinflation is presumably primarily the result of the length changes undergone by the diaphragm in acute hyperinflation. Changes in diaphragmatic geometry are generally considered to be less important in the reduction of the diaphragm's force-generating capacity. Further factors contributing to the mechanical disadvantage in the diaphragm include a reduction in the appositional component of diaphragmatic action (through reduction in the zone of apposition), and a reduction in the insertional component (through a shift in the alignment of the diaphragmatic fibres from axial to radial). In chronic hyperinflation, the diaphragm adapts to the chronically hyperinflated state. This adaptation to chronic foreshortening is similar to the adaptation occurring in the skeletal muscle. It is caused by a dropout of sarcomeres in series along the muscle fibres. It restores the force-generating capacity of the muscle, in part, but it reduces the capacity of the muscle to undergo length changes. The mechanical advantage of the parasternal intercostals and the scalenes is possibly less affected, because the length changes undergone by these muscles during hyperinflation are smaller. The factors determining the mechanical advantage of the parasternal intercostals are complex. Variables related to the mechanical advantage of the parasternal intercostals include: length changes; changes in angle between the parasternal intercostals and the sternum and between rib and sternum; and changes in mechanical arrangement among different parasternals. At present, it is difficult to develop an integrated view of these factors and of their change with hyperinflation. Finally, hyperinflation commonly results in recruitment of expiratory muscles. The functional significance of this expiratory muscle recruitment in patients is still debated.
Mitral valve replacement with Alvarez prosthesis: long-term results
Authors: Y. A. S. Mashhour, J. B. Garcia, M. Ionescu, G. H. Wooler
Journal: Thorax (1969)

The high mortality and morbidity that follow insertion of the Alvarez valve in the mitral position, and particularly the thrombo-embolic complications, stopped us from using it clinically in the Leeds General Infirmary.
Dynamics of eosinophil infiltration in the bronchial mucosa before and after the late asthmatic reaction
Authors: R Aalbers, JG de Monchy, HF Kauffman, M Smith, Y Hoekstra, B Vrugt, W Timens
Journal: European Respiratory Journal (1993)

We wanted to determine whether changes in bronchial hyperresponsiveness (BHR) following allergen challenge show a time relationship with inflammatory events in the airways of allergic asthmatic subjects. Lavage was performed and endobronchial biopsies were taken via the fiberoptic bronchoscope, before, and 3 and 24 h after, allergen challenge, on separate occasions, in nine dual asthmatic responders. The numbers of activated eosinophils, identified by immunohistochemistry, using the monoclonal anti-eosinophil cationic protein antibody, EG2, were significantly increased both at 3 h and at 24 h in the submucosa and bronchial lavage. A significant negative correlation was found between the number of EG2+ cells in the submucosa and in the bronchial lavage 24 h after the allergen challenge (r = -0.70). At 24 h, the amount of eosinophil cationic protein (ECP) was increased in the bronchial lavage. A significant correlation was observed between the amount of ECP at 3 h and the log provocative dose of house dust mite producing a 20% fall in forced expiratory volume in one second (PD20 HDM) (r = -0.63). The results suggest a recruitment of activated eosinophils to the submucosa and, further, to the epithelial lining, followed by degranulation. This process has already started 3 h after allergen challenge, and lasts for at least 24 h, which may result in mucosal damage and subsequent allergen-induced increase in BHR, before and after the late asthmatic reaction.
The National Program for Cancer Chemotherapy
Authors: C. Gordon Zubrod
Journal: JAMA (1972)

In 1955, the National Cancer Institute (NCI) established a national program for cancer chemotherapy.<sup>1</sup>At that time several drugs could effect transient remissions in widespread cancer. However, exploitation of these drug-induced remissions was not possible because the resources required were beyond the capacity of existing instrumentalities, such as the universities and pharmaceutical industry. The intent in 1955 was to organize a drug development program on a valid scientific base, but this could not be done until the precise correlation of drug effects in animals and man was known. Establishment and calibration of the appropriate models took ten years, and based on these correlations, in 1965 NCI instituted its present operation of drug development.<sup>1</sup>Since 1965, NCI has refined this empiric blueprint as dictated by experience and new data.<sup>2,3</sup>The correlations were also used for the definition of the theoretical problems of chemical control of cancer.<sup>1</sup>The
FACTORS WHICH DETERMINE RENAL WEIGHT
Authors: Eaton M. MacKay, Burrell O. Raulston
Journal: The Journal of Experimental Medicine (1931)

THE AMOUNT OF FUNCTIONING RENAL TISSUE AS MEASURED BY THE WEIGHT OF THE KIDNEYS IN THE ALBINO RAT IS DIRECTLY PROPORTIONAL TO THE RENAL FUNCTION AS MEASURED BY THE RATIO: See PDF for the structure under certain special conditions.
Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death
Authors: Noelia Casares, Marie O. Pequignot, Antoine Tesniere, François Ghiringhelli, Stéphan Roux, Nathalie Chaput, Elise Schmitt, Ahmed Hamai, Sandra Hervas-Stubbs, Michel Obeid, Frédéric Coutant, Didier Métivier, Evelyne Pichard, Pierre Aucouturier, Gérard Pierron, Carmen Garrido, Laurence Zitvogel, Guido Kroemer
Journal: The Journal of Experimental Medicine (2005)

Systemic anticancer chemotherapy is immunosuppressive and mostly induces nonimmunogenic tumor cell death. Here, we show that even in the absence of any adjuvant, tumor cells dying in response to anthracyclins can elicit an effective antitumor immune response that suppresses the growth of inoculated tumors or leads to the regression of established neoplasia. Although both antracyclins and mitomycin C induced apoptosis with caspase activation, only anthracyclin-induced immunogenic cell death was immunogenic. Caspase inhibition by Z-VAD-fmk or transfection with the baculovirus inhibitor p35 did not inhibit doxorubicin (DX)-induced cell death, yet suppressed the immunogenicity of dying tumor cells in several rodent models of neoplasia. Depletion of dendritic cells (DCs) or CD8+T cells abolished the immune response against DX-treated apoptotic tumor cells in vivo. Caspase inhibition suppressed the capacity of DX-killed cells to be phagocytosed by DCs, yet had no effect on their capacity to elicit DC maturation. Freshly excised tumors became immunogenic upon DX treatment in vitro, and intratumoral inoculation of DX could trigger the regression of established tumors in immunocompetent mice. These results delineate a procedure for the generation of cancer vaccines and the stimulation of anti-neoplastic immune responses in vivo.
Bacterial neuraminidase facilitates mucosal infection by participating in biofilm production
Authors: Grace Soong, Amanda Muir, Marisa I. Gomez, Jonathan Waks, Bharat Reddy, Paul Planet, Pradeep K. Singh, Yukihiro Kanetko, Matthew C. Wolfgang, Yu Shan Hsiao, Liang Tong, Alice Prince
Journal: Journal of Clinical Investigation (2006)

Many respiratory pathogens, including Hemophilus influenzae, Streptococcus pneumoniae, and Pseudomonas aeruginosa, express neuraminidases that can cleave α2,3-linked sialic acids from glycoconjugates. As mucosal surfaces are heavily sialylated, neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors. However, in contrast to neuraminidase produced by the influenza virus, a role for bacterial neuraminidase in pathogenesis has not yet been clearly established. We constructed a mutant of P. aeruginosa PAO1 by deleting the PA2794 neuraminidase locus (Δ2794) and tested its virulence and immunostimulatory capabilities in a mouse model of infection. Although fully virulent when introduced i.p., the Δ2794 mutant was unable to establish respiratory infection by i.n. inoculation. The inability to colonize the respiratory tract correlated with diminished production of biofilm, as assessed by scanning electron microscopy and in vitro assays. The importance of neuraminidase in biofilm production was further demonstrated by showing that viral neuraminidase inhibitors in clinical use blocked P. aeruginosa biofilm production in vitro as well. The P. aeruginosa neuraminidase has a key role in the initial stages of pulmonary infection by targeting bacterial glycoconjugates and contributing to the formation of biofilm. Inhibiting bacterial neuraminidases could provide a novel mechanism to prevent bacterial pneumonia.
Downregulation of tumor necrosis factor (TNF) sensitivity via modulation of TNF binding capacity by protein kinase C activators.
Authors: R Unglaub, B Maxeiner, B Thoma, K Pfizenmaier, P Scheurich
Journal: The Journal of Experimental Medicine (1987)

The regulatory action of activators for protein kinase C on the specific binding capacity for recombinant human tumor necrosis factor alpha (TNF-alpha) was studied on various human cell lines. Phorbol myristate acetate (PMA) and oleyl acetyl glycerol (OAG) both are able to rapidly downregulate TNF-binding capacity of normal and malignant cells derived from various tissues. As PMA treatment did not enhance internalization of TNF-alpha-receptor complexes at 37 degrees C, and since OAG was able to downregulate TNF-binding capacity under conditions where internalization and shedding of receptor protein are prevented, we conclude that protein kinase C controls ligand affinity of the TNF-receptor protein, possibly via direct phosphorylation. Protein kinase C triggered downregulation of TNF-alpha-binding capacity concomitantly resulted in reduction of TNF-alpha sensitivity, as revealed from decreased cytotoxic action of TNF-alpha on L 929 cells and from inhibition of TNF-alpha-mediated enhancement of HLA class II antigen expression in Colo 205 cells. Restoration of TNF-binding capacity upon abrogation of protein kinase C stimulation leads to full recovery of TNF responsiveness, further supporting the close linkage of TNF-receptor expression and TNF sensitivity. These data suggest that regulation of TNF-binding capacity by protein kinase C is one of the cellular control mechanisms of TNF responsiveness.
Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model.
Authors: P Costelli, N Carbó, L Tessitore, G J Bagby, F J Lopez-Soriano, J M Argilés, F M Baccino
Journal: Journal of Clinical Investigation (1993)

Rats bearing the Yoshida AH-130 ascites hepatoma showed enhanced fractional rates of protein degradation in gastrocnemius muscle, heart, and liver, while fractional synthesis rates were similar to those in non-tumor bearing rats. This hypercatabolic pattern was associated with marked perturbations of the hormonal homeostasis and presence of tumor necrosis factor in the circulation. The daily administration of a goat anti-murine TNF IgG to tumor-bearing rats decreased protein degradation rates in skeletal muscle, heart, and liver as compared with tumor-bearing rats receiving a nonimmune goat IgG. The anti-TNF treatment was also effective in attenuating early perturbations in insulin and corticosterone homeostasis. Although these results suggest that tumor necrosis factor plays a significant role in mediating the changes in protein turnover and hormone levels elicited by tumor growth, the inability of such treatment to prevent a reduction in body weight implies that other mediators or tumor-related events were also involved.
Cell-to-cell contact of activated mast cells with fibroblasts and lymphocytes in systemic sclerosis
Authors: Thomas Hügle, Kathryn White, Jacob M van Laar
Journal: Annals of the Rheumatic Diseases (2012)

Mast cells (MC) are bone marrow derived granulated cells which mature and reside within the connective tissue. MC can release a variety of preformed mediators such as histamine, proteases, cytokines, growth factors and proteoglycans by degranulation.1 In inflammation, activated MC orchestrate the infiltration of leucocytes2 ,3 and present antigen to lymphocytes.4 MC directly activate fibroblasts via gap junctions5 and coculture of MC with fibroblasts in vitro stimulates collagen production and enhances collagen contraction.6 MC also regulate the proliferation of neighbouring fibroblasts. This effect is dependent on heterotypic cell-to-cell contact and requires the release of interleukin (IL)-4 by MC.7

MC have been implicated in systemic sclerosis (SSc) pathology based on their increased numbers and degranulation in skin.8 We showed recently that MC are a main source of transforming growth factor-β, a major profibrotic mediator.9 In order to …
HIGH FREQUENCY OF EPSTEIN-BARR VIRUS GENOME IN HIV-POSITIVE PATIENTS WITH HODGKIN'S DISEASE
Authors: Stefania Uccini, Francesca Monardo, LuigiP. Ruco, CarloD. Baroni, Alberto Faggioni, AnnaM. Agliano, Angela Gradilone, Vittorio Manzari, Luca Vago, Giulio Gostanzi, Antonino Carbone, Mauro Boiocchi, Vally De Re
Journal: The Lancet (1989)
Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D
Authors: Hanno Bolz, Benigna von Brederlow, Alfredo Ramírez, Elizabeth C. Bryda, Kerstin Kutsche, Hans Gerd Nothwang, Mathias Seeliger, Maria del C.-Salcedó Cabrera, Manuel Caballeró Vila, Orfilio Pelaez Molina, Andreas Gal, Christian Kubisch
Journal: Nature Genetics (2001)
The fodrin-ankyrin cytoskeleton of choroid plexus preferentially colocalizes with apical Na+K(+)-ATPase rather than with basolateral anion exchanger AE2.
Authors: S L Alper, A Stuart-Tilley, C F Simmons, D Brown, D Drenckhahn
Journal: Journal of Clinical Investigation (1994)

A unique feature of the choroid plexus as a single-layer epithelium is its localization of Na+K(+)-ATPase at its apical (lumenal) surface. In contrast, a band 3 (AE1)-related anion exchanger protein has been localized to the basolateral surface of the choroid plexus. Both Na+K(+)-ATPase and AE1 in other tissues have been shown to bind via ankyrin to the spectrin-actin-based membrane cytoskeleton. Since linkage of integral membrane proteins to the membrane cytoskeleton is important for their restriction to specialized domains of the cell surface, we investigated the polarity of the choroid plexus membrane cytoskeleton. We developed isoform-specific antibodies to confirm the identity of choroid plexus band 3-related polypeptide as AE2. We demonstrated that ankyrin, fodrin/spectrin, actin, myosin, and alpha-actinin are predominantly apical in choroid plexus and preferentially colocalize with apical Na+K(+)-ATPase rather than with basolateral anion exchanger AE2. Colchicine administration did not alter the polarity of apical cytoskeletal and transport proteins or basolateral AE2 in choroid plexus, suggesting that biosynthetic targeting of these proteins is not microtubule dependent. In choroid plexus papilloma, Na+K(+)-ATPase and AE2 were decreased in amount and failed to preserve their polarized distributions.
Proteomic Analysis to Identify Breast Cancer Biomarkers in Nipple Aspirate Fluid
Authors: Hannah Alexander, Andrew L. Stegner, Colette Wagner-Mann, Garrett C. Du Bois, Stephen Alexander, Edward R. Sauter
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Proteomic analysis of breast nipple aspirate fluid (NAF) holds promise as a noninvasive method to identify markers of breast cancer. The objectives of the study were to: (a) describe the NAF proteome, (b) identify candidate markers of breast cancer in NAF by using proteomic analysis, and (c) validate the markers identified by using a quantitative, high-throughput ELISA analysis. Experimental Design: For proteome analysis, NAF proteins from a single subject without breast cancer were separated by two-dimensional PAGE and were subjected to matrix-assisted laser desorption ionization time-of-flight mass spectometry identification. A total of 41 different proteins were identified, 25 of which were known to be secreted. To identify breast cancer markers, we separated 20 NAF samples (10 normal, 10 cancer) by two-dimensional PAGE. Three protein spots were detected that were up-regulated in three or more cancer samples. These spots were identified to be gross cystic disease fluid protein (GCDFP)-15, apolipoprotein D (apoD), and α1-acid glycoprotein (AAG). To validate these three potential biomarkers, 105 samples (53 from benign breasts and 52 from breasts with cancer) were analyzed using ELISA. Results: Among all of the subjects, GCDFP-15 levels were lower (P &amp;lt; 0.001) and AAG levels were higher (P = 0.001) in breasts with cancer. This was also true in premenopausal (GCDFP-15, P = 0.011; AAG, P = 0.002) but not in postmenopausal women. GCDFP-15 levels were lowest (P = 0.003) and AAG levels highest (P &amp;lt; 0.001) in women with ductal carcinoma in situ (DCIS). Menopausal status influenced GCDFP-15 and AAG more in women without breast cancer than in women with breast cancer. apoD levels did not correlate significantly with breast cancer. Conclusions: Our study revealed that the NAF proteome, as defined by two-dimensional PAGE, consists of a limited number of proteins, and that the expression of AAG and GCDFP-15 correlates with disease presence and stage.
Osteotomy in a Man of Forty-Two
Authors: W. C. Brown
Journal: BMJ (1896)

pearance of the eruption rather confirmed her statement in that it looked recent), it would seem that varicella may be in- fectious before the outcome of the rash.W. C. gave rise to the following cases.He was at once removed from the ward; but CASE II, G. W., developed varicella on November 15th, incubation period at least thirteen days.G. W. was at once removed from the ward.He probably, however, infected:CASE 1II, W. E., who developed varicella November 27th, incubation period at least twelve days; CASE iv, H. Fi., who developed varicella on December 3rd, incubation period at least
Perioperative Increases in Serum Creatinine Are Predictive of Increased 90-Day Mortality After Coronary Artery Bypass Graft Surgery
Authors: Jeremiah R. Brown, Richard P. Cochran, Lawrence J. Dacey, Cathy S. Ross, Karyn S. Kunzelman, Robert F. Dunton, John H. Braxton, David C. Charlesworth, Robert A. Clough, Robert E. Helm, Bruce J. Leavitt, Todd A. MacKenzie, Gerald T. O’Connor
Journal: Circulation (2006)

Background— Impaired renal function after coronary artery bypass graft (CABG) surgery is a key risk factor for in-hospital mortality. However, perioperative increases in serum creatinine and the association with mortality has not been well-studied. We assessed the hypothesis that perioperative increases in creatinine are associated with increased 90-day mortality. Methods and Results— We studied 1391 patients in northern New England undergoing CABG in 2001 and evaluated preoperative and postoperative creatinine. Patients with preoperative dialysis were excluded. Data were linked to the National Death Index to assess 90-day survival. Kaplan-Meier and log-rank techniques were used. Patients were stratified by percent increase in creatinine from baseline: &lt;25%, 25% to 49%, 50% to 99%, ≥100%. We assessed 90-day survival and calculated adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for creatinine groups, adjusting for age and sex. Patients with the largest creatinine increases (50% to 99% or ≥100%) had significantly higher 90-day mortality compared with patients with a smaller increase (&lt;50%; P &lt;0.001). Adjusted HR and 95% CI confirmed patients in the higher 2 groups had an increased risk of mortality compared with the &lt;25% (referent); however, the 25% to 49% group was not different from the referent: 1.80 (95% CI: 0.73 to 4.44), 6.57 (95% CI, 3.03 to 14.27), and 22.10 (95% CI, 11.25 to 43.39). Conclusions— Patients with large creatinine increases (≥50%) after CABG surgery have a higher 90-day mortality compared with patients with small increases. Efforts to identify patients with impaired renal function and to preserve renal function before cardiac surgery may yield benefits for patients in the future.
The essence of cognitive development
Authors: John P. Spencer
Journal: Behavioral and Brain Sciences (2001)

Psychologists have long debated the underlying cause of infants' perseverative reaching. Thelen et al. explain the error in terms of general processes that make goal-directed actions to remembered locations. The context- and experience-dependent nature of their model implies that there is no single cause of the A-not-B error, and, more generally, no core essence to cognitive development.
Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes.
Authors: J T Sanderson, R J Letcher, M Heneweer, J P Giesy, M van den Berg
Journal: Environmental Health Perspectives (2001)

We investigated a potential mechanism for the estrogenic properties of three chloro-s-triazine herbicides and six metabolites in vitro in several cell systems. We determined effects on human aromatase (CYP19), the enzyme that converts androgens to estrogens, in H295R (adrenocortical carcinoma), JEG-3 (placental choriocarcinoma), and MCF-7 (breast cancer) cells; we determined effects on estrogen receptor-mediated induction of vitellogenin in primary hepatocyte cultures of adult male carp (Cyprinus carpio). In addition to atrazine, simazine, and propazine, two metabolites--atrazine-desethyl and atrazine-desisopropyl--induced aromatase activity in H295R cells concentration-dependently (0.3-30 microM) and with potencies similar to those of the parent triazines. After a 24-hr exposure to 30 microM of the triazines, an apparent maximum induction of about 2- to 2.5-fold was achieved. The induction responses were confirmed by similar increases in CYP19 mRNA levels, determined by reverse-transcriptase polymerase chain reaction. In JEG-3 cells, where basal aromatase expression is about 15-fold greater than in H295R cells, the induction responses were similar but less pronounced; aromatase expression in MCF-7 cells was neither detectable nor inducible under our culture conditions. The fully dealkylated metabolite atrazine-desethyl-desisopropyl and the three hydroxylated metabolites (2-OH-atrazine-desethyl, -desisopropyl, and -desethyl-desisopropyl) did not induce aromatase activity. None of the triazine herbicides nor their metabolites induced vitellogenin production in male carp hepatocytes; nor did they antagonize the induction of vitellogenin by 100 nM (EC(50) 17beta-estradiol. These findings together with other reports indicate that the estrogenic effects associated with the triazine herbicides in vivo are not estrogen receptor-mediated, but may be explained partly by their ability to induce aromatase in vitro.