tbuckley/cabot-search huggingface dataset:
Relationship between transdiaphragmatic and mouth twitch pressures at functional residual capacity
Authors: F Laghi, MJ Tobin
Journal: European Respiratory Journal (1997)

The clinical application of transdiaphragmatic twitch pressure (Pdi,tw) response to phrenic nerve stimulation has been hindered by the requirement for placement of oesophageal and gastric balloons. Investigators have reported that mouth twitch pressure (Pmo,tw) estimates Pdi,tw accurately at lung volumes above and below functional residual capacity (FRC). However, it is not known whether Pmo,tw estimates Pdi,tw accurately when stimulation is performed at FRC during relaxed conditions. The aim of this study was to develop a simple method whereby measurements of Pmo could be used to predict oesophageal twitch pressure (Poes,tw) and possibly Pdi,tw at FRC. The study was performed in 11 healthy volunteers during phrenic nerve stimulation. At FRC, 9 of the 11 subjects showed a poor correlation between Pmo,tw and Poes,tw, and between Pmo,tw and Pdi,tw, probably due to varying degrees of glottic closure. Stimulations performed while subjects maintained an inspiratory flow of approximately 50 mL x s(-1), or at the point of reattaining FRC during an inspiration preceded by a limited exhalation, produced good correlations between Pmo,tw and Poes,tw (r=0.97 in both instances) and Pmo,tw and Pdi,tw (r=0.96 and r=0.95, respectively), with a steep slope. The respective slopes for the Pmo,tw Poes,tw relationship were 0.88 and 0.94, and for the Pmo,tw Pdi,tw relationship, 0.59 and 0.54. Unfortunately, these manoeuvres produced a significant increase in transpulmonary pressure (3.6+/-0.6 (SE) and 5.6+/-1.4 cmH2O, respectively), suggesting change in diaphragmatic length. Stimulations delivered while subjects performed an inspiratory effort or during exhalation against a high resistance preceded by a limited inhalation could not be used to predict Poes,tw and Pdi,tw from Pmo,tw. In conclusion, although transdiaphragmatic and oesophageal twitch pressure could be predicted from mouth twitch pressure during some inspiratory manoeuvres mouth twitch pressure was not reliable for the prediction of the oesophageal and transdiaphragmatic twitch pressure at functional residual capacity during relaxed conditions in healthy volunteers.
Glycemic Control, Coping, and Internalizing and Externalizing Symptoms in Adolescents With Type 1 Diabetes
Authors: Koen Luyckx, Inge Seiffge-Krenke, Sarah E. Hampson
Journal: Diabetes Care (2010)

This study examines how active coping and withdrawal, psychological (internalizing and externalizing) symptoms, and glycemic control (A1C values) influence each other across time in adolescents with type 1 diabetes.One hundred and nine adolescents participated in a four-wave longitudinal study spanning four years (mean age at Time 1 was 13.77). Patients were visited at home and completed questionnaires measuring coping and psychological symptoms. The treating physicians were contacted to obtain A1C values. Cross-lagged path analysis from a structural equation modeling approach was used for data analysis.Clinically meaningful pathways between coping and glycemic control were found across time. Active coping prospectively predicted lower A1C levels, which, in turn, predicted active coping. Higher A1C levels and higher psychological symptoms consistently predicted avoidance coping across time. Finally, psychological symptomatology constituted an important link in the observed longitudinal chain of effects. More specifically, higher A1C values and symptomatology at Time 1 positively predicted withdrawal at Time 2, which, in turn, positively predicted symptomatology at Time 3. Next, symptomatology at Time 3 positively predicted higher A1C values at Time 4, thus coming full circle.Coping with everyday stress, psychological symptoms, and glycemic control were interrelated across time. Evidence was obtained for reciprocal pathways and mutually reinforcing mechanisms, indicating the need to monitor coping strategies and psychological symptoms along with glycemic control in optimizing clinical care in adolescents with type 1 diabetes.
Increasing Incidence of Testicular Germ Cell Tumors Among Black Men in the United States
Authors: Katherine A. McGlynn, Susan S. Devesa, Barry I. Graubard, Philip E. Castle
Journal: Journal of Clinical Oncology (2005)

There has been marked disparity in the incidence of testicular germ cell tumors (TGCT) among white and black men for a number of decades in the United States. Since at least the beginning of the Surveillance, Epidemiology, and End Results (SEER) Program in 1973, incidence rates among white men have been five times higher than rates among black men. In addition, rates among white men have been increasing, whereas rates among black men have remained stable. However, a recent examination of ethnic-specific rates suggested that the incidence among black men may have begun to change in the 1990s.
The effects of gemfibrozil upon the metabolism of chylomicron-like emulsions in patients with endogenous hypertriglyceridemia
Authors: R Santos
Journal: Cardiovascular Research (2001)

Objective: To evaluate the effects of gemfibrozil upon the intravascular metabolism of chylomicron-like emulsions in endogenous hypertriglyceridemia. Methods: We evaluated the plasma kinetics of a chylomicron-like emulsion in 39 subjects: 27 hypertriglyceridemics, total cholesterol (TC) expressed as median (%25; %75) 7.47 (6.1; 8.19) mmol/l and plasma triglycerides (TG) 4.28 (3.6; 18.5) mmol/l and in 12 normolipidemics, TC 4.7 (3.85; 5.37) mmol/l and TG 0.91 (0.64; 1.75) mmol/l. Hypertriglyceridemics were evaluated at baseline and after a 30-day 1200-mg/day gemfibrozil (n = 8) or placebo treatment (n = 7). The emulsion labelled with 14C-cholesteryl oleate (14C-CO) and 3H-triolein (3H-TO) was injected intravenously after a 12-h fast. The plasma kinetics of 3H-TO and 14C-CO were determined to assess, respectively, lipolysis and clearance of chylomicron and remnants by compartmental analysis. Results: The residence times (in minutes) of 3H-TO and 14C-CO of hypertriglyceridemics were roughly twice the values of normolipidemics, i.e. 8.0 (5.5; 12.0) versus 15.0 (11.0; 24.0) and 21.5 (14.0; 33.0) versus 44.0 (32.0; 72.0), P = 0.001. Gemfibrozil treatment of hypertriglyceridemic patients reduced the residence times of 3H-TO and 14C-CO, respectively, by 46% (P = 0.003) and 53% (P = 0.008). Effects were noted on the slow phase of emulsion plasma removal, which was reduced in hypertriglyceridemics. After treatment, the emulsion residence times determined in hypertriglyceridemics attained the values of the normolipidemic group. Conclusions: Gemfibrozil treatment normalised the defects in chylomicron-like emulsion catabolism observed in endogenous hypertriglyceridemia patients.
Comment on: Lassenius et al. Bacterial Endotoxin Activity in Human Serum Is Associated With Dyslipidemia, Insulin Resistance, Obesity, and Chronic Inflammation. Diabetes Care 2011;34:1809–1815
Authors: Sobha Rani Koduru, Smitha Achuthankutty, Husam Ghanim, Paresh Dandona
Journal: Diabetes Care (2012)

Lassenius et al. (1) have shown that high serum endotoxin activity is associated with components of metabolic syndrome. An important observation in their analysis is that most diabetic patients with high serum lipopolysaccharide (LPS) activity had elevated serum triglyceride and low HDL cholesterol concentrations and that serum LPS activity correlated positively with C-reactive protein, a marker for low-grade inflammation. The data presented is impressive; however, the source of endotoxemia was not clearly postulated. Also the exact composition of the diet consumed by the subjects was not mentioned. We think this information is significant because research has shown that certain diets induce inflammation and LPS production.

Our studies showed that a high-fat, high-carbohydrate meal (HFHC, …
Zanvil Alexander Cohn 1926-1993.
Authors: R M Steinman, C L Moberg
Journal: The Journal of Experimental Medicine (1994)

Zanvil Alexander Cohn, an editor of this Journal since 1973, died suddenly on June 28, 1993. Cohn is best known as the father of the current era of macrophage biology. Many of his scientific accomplishments are recounted here, beginning with seminal studies on the granules of phagocytes that were performed with his close colleague and former editor of this Journal, James Hirsch. Cohn and Hirsch identified the granules as lysosomes that discharged their contents of digestive enzymes into vacuoles containing phagocytosed microbes. These findings were part of the formative era of cell biology and initiated the modern study of endocytosis and cell-mediated resistance to infection. Cohn further explored the endocytic apparatus in pioneering studies of the mouse peritoneal macrophage in culture. He described vesicular inputs from the cell surface and Golgi apparatus and documented the thoroughness of substrate digestion within lysosomal vacuoles that would only permit the egress of monosaccharides and amino acids. These discoveries created a vigorous environment for graduate students, postdoctoral fellows, and junior and visiting faculty. Some of the major findings that emerged from Cohn's collaborations included the radioiodination of the plasma membrane for studies of composition and turnover; membrane recycling during endocytosis; the origin of the mononuclear phagocyte system in situ; the discovery of the dendritic cell system of antigen-presenting cells; the macrophage as a secretory cell, including the release of proteases and large amounts of prostaglandins and leukotrienes; several defined parameters of macrophage activation, especially the ability of T cell-derived lymphokines to enhance killing of tumor cells and intracellular protozoa; the granule discharge mechanism whereby cytotoxic lymphocytes release the pore-forming protein perforin; the signaling of macrophages via myristoylated substrates of protein kinase C; and a tissue culture model in which monocytes emigrate across tight endothelial junctions. In 1983, Cohn turned to a long-standing goal of exploring host resistance directly in humans. He studied leprosy, focusing on the disease site, the parasitized macrophages of the skin. He injected recombinant lymphokines into the skin and found that these molecules elicited several cell-mediated responses. Seeing this potential to enhance host defense in patients, Cohn was extending his clinical studies to AIDS and tuberculosis. Zanvil Cohn was a consummate physician-scientist who nurtured the relationship between cell biology and infectious disease.(ABSTRACT TRUNCATED AT 400 WORDS)
Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium
Authors: Richard A Stabler, Miao He, Lisa Dawson, Melissa Martin, Esmeralda Valiente, Craig Corton, Trevor D Lawley, Mohammed Sebaihia, Michael A Quail, Graham Rose, Dale N Gerding, Maryse Gibert, Michel R Popoff, Julian Parkhill, Gordon Dougan, Brendan W Wren
Journal: Genome biology (2009)

Abstract Background The continued rise of Clostridium difficile infections worldwide has been accompanied by the rapid emergence of a highly virulent clone designated PCR-ribotype 027. To understand more about the evolution of this virulent clone, we made a three-way genomic and phenotypic comparison of an 'historic' non-epidemic 027 C. difficile (CD196), a recent epidemic and hypervirulent 027 (R20291) and a previously sequenced PCR-ribotype 012 strain (630). Results Although the genomes are highly conserved, the 027 genomes have 234 additional genes compared to 630, which may contribute to the distinct phenotypic differences we observe between these strains relating to motility, antibiotic resistance and toxicity. The epidemic 027 strain has five unique genetic regions, absent from both the non-epidemic 027 and strain 630, which include a novel phage island, a two component regulatory system and transcriptional regulators. Conclusions A comparison of a series of 027 isolates showed that some of these genes appeared to have been gained by 027 strains over the past two decades. This study provides genetic markers for the identification of 027 strains and offers a unique opportunity to explain the recent emergence of a hypervirulent bacterium.
Glycogen Storage Diseases Presenting as Hypertrophic Cardiomyopathy
Authors: Michael Arad, Barry J. Maron, Joshua M. Gorham, Walter H. Johnson, J. Philip Saul, Antonio R. Perez-Atayde, Paolo Spirito, Gregory B. Wright, Ronald J. Kanter, Christine E. Seidman, J.G. Seidman
Journal: New England Journal of Medicine (2005)

Unexplained left ventricular hypertrophy often prompts the diagnosis of hypertrophic cardiomyopathy, a sarcomere-protein gene disorder. Because mutations in the gene for AMP-activated protein kinase gamma2 (PRKAG2) cause an accumulation of cardiac glycogen and left ventricular hypertrophy that mimics hypertrophic cardiomyopathy, we hypothesized that hypertrophic cardiomyopathy might also be clinically misdiagnosed in patients with other mutations in genes regulating glycogen metabolism.Genetic analyses performed in 75 consecutive unrelated patients with hypertrophic cardiomyopathy detected 40 sarcomere-protein mutations. In the remaining 35 patients, PRKAG2, lysosome-associated membrane protein 2 (LAMP2), alpha-galactosidase (GLA), and acid alpha-1,4-glucosidase (GAA) genes were studied.Gene defects causing Fabry's disease (GLA) and Pompe's disease (GAA) were not found, but two LAMP2 and one PRKAG2 mutations were identified in probands with prominent hypertrophy and electrophysiological abnormalities. These results prompted the study of two additional, independent series of patients. Genetic analyses of 20 subjects with massive hypertrophy (left ventricular wall thickness, > or =30 mm) but without electrophysiological abnormalities revealed mutations in neither LAMP2 nor PRKAG2. Genetic analyses of 24 subjects with increased left ventricular wall thickness and electrocardiograms suggesting ventricular preexcitation revealed four LAMP2 and seven PRKAG2 mutations. Clinical features associated with defects in LAMP2 included male sex, severe hypertrophy, early onset (at 8 to 17 years of age), ventricular preexcitation, and asymptomatic elevations of two serum proteins.LAMP2 mutations typically cause multisystem glycogen-storage disease (Danon's disease) but can also present as a primary cardiomyopathy. The glycogen-storage cardiomyopathy produced by LAMP2 or PRKAG2 mutations resembles hypertrophic cardiomyopathy but is distinguished by electrophysiological abnormalities, particularly ventricular preexcitation.
Critical Impact of Radiotherapy Protocol Compliance and Quality in the Treatment of Advanced Head and Neck Cancer: Results From TROG 02.02
Authors: Lester J. Peters, Brian O'Sullivan, Jordi Giralt, Thomas J. Fitzgerald, Andy Trotti, Jacques Bernier, Jean Bourhis, Kally Yuen, Richard Fisher, Danny Rischin
Journal: Journal of Clinical Oncology (2010)

Purpose To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer. Patients and Methods The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality. Results At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center (&lt; five patients, 29.8%; ≥ 20 patients, 5.4%; P &lt; .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): −2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P &lt; .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P &lt; .001, respectively. Conclusion These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems.
<i>CCR</i> 20th Anniversary Commentary: Vorinostat—Gateway to Epigenetic Therapy
Authors: Wm. Kevin Kelly, Paul Marks, Victoria M. Richon
Journal: Clinical Cancer Research (2015)

Abstract The study by Kelly and colleagues, published in the September 1, 2003, issue of Clinical Cancer Research, established the safety and biologic activity of the first-in-class histone deacetylase inhibitor, vorinostat, which was administered intravenously. Subsequent studies led to the development of oral vorinostat and the regulatory approval of vorinostat for cutaneous T-cell lymphomas, which opened the door for the next generation of inhibitors. Clin Cancer Res; 21(10); 2198–200. ©2015 AACR. See related article by Kelly et al., Clin Cancer Res 2003;9(10) September 1, 2003;3578–88
Molecular and Functional Identification of m <sub>1</sub> Muscarinic Acetylcholine Receptors in Rat Ventricular Myocytes
Authors: Virendra K. Sharma, Henry M. Colecraft, David X. Wang, Allan I. Levey, Elena V. Grigorenko, Hermes H. Yeh, Shey-Shing Sheu
Journal: Circulation Research (1996)

The expression of muscarinic acetylcholine receptor (mAChR) subtypes in freshly isolated adult rat ventricular myocytes was investigated by reverse transcription of cellular mRNA followed by amplification of cDNA using the polymerase chain reaction (PCR). After reverse-transcriptase PCR, bands were obtained corresponding to the expected sizes for the m 1 and m 2 but not for the m 3 to m 5 mAChRs. The identity of the m 1 and m 2 bands was confirmed by single-cell PCR, restriction digest mapping, and Southern blot analysis. The presence of m 1 and m 2 , but not m 3 , mAChR protein in these cells was shown by indirect immunofluorescence studies using subtype-specific antibodies. It was further investigated whether the identified m 1 mAChR was responsible for the stimulatory effects on Ca 2+ transients by high concentrations of carbachol (&gt;10 μmol/L) known to occur in these cells. In pertussis toxin–treated ventricular myocytes electrically stimulated at 1 Hz, carbachol (300 μmol/L) increased the basal Ca 2+ level from 96±7 to 118±8 nmol/L and the peak Ca 2+ transient level from 519±32 to 640±36 nmol/L (mean±SEM, P &lt;.05 for both, n=8). These effects of carbachol on Ca 2+ transients were antagonized by 10 nmol/L pirenzepine, an m 1 mAChR–selective antagonist. In contrast, the m 2 mAChR–selective antagonist methoctramine (up to 100 nmol/L) did not inhibit the response. These results are the first to use single-cell PCR to probe cardiomyocyte-specific gene expression and indicate that m 1 mAChRs are expressed on adult rat ventricular myocytes in addition to m 2 mAChRs. The results further suggest that m 1 mAChRs mediate the stimulatory responses on Ca 2+ transients to high concentrations of cholinergic agonists seen in these cells.
Phosphoglucose Isomerases of Hagfish, Zebrafish, Gray Mullet, Toad, and Snake, with Reference to the Evolution of the Genes in Vertebrates
Authors: Hsiao-wei Kao, Sin-Che Lee
Journal: Molecular Biology and Evolution (2002)

Phosphoglucose isomerase (PGI) is a protein with multiple functions. To infer its structure changes and evolution in vertebrates, we cloned cDNAs encoding PGI genes from hagfish (Paramyxine yangi), gray mullet (Mugil cephalus), zebrafish (Danio rerio), toad (Bufo melanosticus), and snake (Boiga kraepelini). Only one PGI gene was cloned in each of hagfish, toad, and snake, but two PGI genes were found in zebrafish and gray mullet, respectively. The PGI of hagfish encodes 554 amino acids, in contrast to the PGIs of bonyfishes, toad, and snake which encode 553 amino acids and the PGIs of mammals which encode 558 amino acids. Among 558 aligned amino acid sites, there are 314 sites (56.27%) totally conserved. To see if diversifying selection acts on PGI amino acids of vertebrates, we calculated the pairwise ratio of nonsynonymous versus synonymous substitution per site (Ka/Ks) and the ratio of radical amino acid changes versus conservative amino acid changes per sites (dR/dC) between PGI sequences. The average pairwise ratio between nonsynonymous substitutions per nucleotide (Ka) and synonymous substitutions per nucleotide (Ks) among vertebrate PGI sequences equals 0.047 ± 0.019. The average pairwise ratio between radical amino acid changes and conservative amino acid changes (dR/dC) among the vertebrate PGIs equal 0.938 ± 0.158 for charge changes, 0.558 ± 0.085 for polarity changes, and 0.465 ± 0.0714 when both polarity and volume are considered. There is no amino acid within the vertebrate PGIs under diversifying selection as analyzed by the method of Yang et al. (2000b) . The results suggest that the present vertebrate PGIs are at evolutionary stasis and are being subjected to intense purifying selection. The purifying selection is to maintain polarity and volume of the protein but not the charge groups of amino acids. Phylogenetic analysis reveals that vertebrate PGIs can be classified into three major groups: the mammalian, amphibian-reptilian, and teleostean PGIs. The gene tree suggests that the gene duplication event of PGI in bonyfishes occurred before diversification of Acanthopterygii but after the split of bonyfishes and tetrapods. The evolution of multiple functions of PGI is discussed.
Social incoherence and the narrative construction of memory
Authors: Judith Pintar, Steven Jay Lynn
Journal: Behavioral and Brain Sciences (2006)

By shifting the focus of analysis from forgetting and remembering to interpreting and making-meaning, Erdelyi allows theoretical consideration of repression to move beyond the heuristic assumption that personal memory is necessarily private memory. In this commentary, repression is considered to be a collective process in which memories are shaped by the need for coherence between individual and social narratives.
ACUTE INFLAMMATION AND TISSUE MAST CELLS IN ADRENALECTOMIZED RATS WITH CUTANEOUS MUCORMYCOSIS
Authors: Samuel H. Paplanus, Walter H. Sheldon
Journal: The Journal of Experimental Medicine (1963)

The effects of the absence of adrenal tissues on the inflammatory reaction and on the relationship of the tissue mast cells to the inflammatory process have been studied histologically in rats with cutaneous Rhizopus oryzae infection. Degranulation and regranulation of the tissue mast cells at the site of injury have been found to correlate respectively with the onset and subsidence of the exudative cellular phase of inflammation. In the adrenalectomized animals regranulation of these cells and correspondingly termination of the exudative phase are delayed. In the lesions of these rats the numbers of eosinophiles are increased. The proliferative cellular processes of inflammation, although delayed in onset, progress in essentially normal manner but result in some increased collagen deposition. The lack of adrenal secretions does not enhance fungus proliferation and is not associated with spread of the infection. In the present experiments the effectiveness of inflammation does not differ in normal and adrenalectomized rats.