tbuckley/cabot-search huggingface dataset:
Mucociliary clearance in cystic fibrosis knockout mice infected with Pseudomonas aeruginosa
Authors: EA Cowley, CG Wang, D Gosselin, D Radzioch, DH Eidelman
Journal: European Respiratory Journal (1997)

In this study, we examined whether mucociliary clearance differed between cystic fibrosis (CF) knockout mice and wildtype controls. Additionally, we investigated whether infection with Pseudomonas aeruginosa, a common pathogen in the CF lung, affected this important host defence mechanism. Ciliary beat frequency (fcb) and particle transport (PT) were recorded using an in vitro lung explant preparation. Measurements were made from uninfected cystic fibrosis transmembrane conductance regulator (CFTR) knockout (-/-) mice and littermate controls (+/+) and compared to measurements from infected animals. While there were no differences detectable in fcb between CFTR -/- mice and their +/+ controls either in the presence or absence of P. aeruginosa, PT rates were different between these groups; interestingly, PT rates appeared dependent on both CFTR and infection status, with uninfected CFTR +/+ animals demonstrating higher rates of PT than their -/- littermates, while CFTR +/+ P. aeruginosa-infected mice demonstrated lower PT than knockout mice. These data demonstrate differences in mucociliary clearance between cystic fibrosis transmembrane conductance regulator knockout mice and controls, and further that Pseudomonas aeruginosa infection affects mucociliary clearance in the peripheral airways of mice. Additionally, the observed differences in particle transport suggest that cystic fibrosis transmembrane conductance regulator knockout mice demonstrate different mucociliary responses to infection.
Cell permeability, sodium transport, and the hypertensive process in the rat.
Authors: S M Friedman, C L Friedman
Journal: Circulation Research (1976)

The tail artery of the spontaneously hypertensive rat (SHR) (Carworth Farms), excised rapidly and immersed immediately in cold (2 degrees C) Li-substituted physiologic salt solution (LiPSS), continues to exchange cell Na+ and K+ for Li+, this exchange is negligible to the control (Carworth Farms normotensive) CFN). In the incubated artery at 37 degrees C, when the vascular smooth muscle cell is slack, the leakiness of the cell membrane in the SHR is more than offset by increased Na+ pumping activity, so that cell Na+ is subnormal. A high precision technique with ion-specific electrodes was developed to follow the passive downhill and active uphill phases of Na+-K+ exchange in the perfused artery exposed to K+-free physiologic salt solution (K+-free PSS) followed by physiological salt solution (PSS). The exchange was found to be fully reversible and sufficiently equimolar to be definable in terms of movements of K+ alone. The rates of ionic movement across the vascular smooth muscle cell were found to be about 6 times faster for the vessel perfused at low pressure (less than 3 mm Hg) than for the slack incubated artery. The rate of passive downhill movement was significantly accelerated in the mature SHR compared with CFN, and the net active transport activity much enhanced. Similar changes were seen as early as 3 weeks after treatment with DOCA and were pronounced at 8 weeks. It is proposed that conditions favoring a sustained accumulation of Na+ in the vascular smooth muscle cell are countered by an enhanced synthesis of transport protein, of contractile protein, and of paracellular matrix protein which progressively restructure the wall.
Thymidylate Synthase and Excision Repair Cross-Complementing Group-1 as Predictors of Responsiveness in Mesothelioma Patients Treated with Pemetrexed/Carboplatin
Authors: Paolo Andrea Zucali, Elisa Giovannetti, Annarita Destro, Manlio Mencoboni, Giovanni Luca Ceresoli, Letizia Gianoncelli, Elena Lorenzi, Fabio De Vincenzo, Matteo Simonelli, Matteo Perrino, Andrea Bruzzone, Erik Thunnissen, Gianni Tunesi, Laura Giordano, Massimo Roncalli, Godefridus J. Peters, Armando Santoro
Journal: Clinical Cancer Research (2011)

The pemetrexed/platinum agent combination represents the standard of care in first-line treatment for malignant pleural mesothelioma (MPM). However, there are no established indicators of responsiveness that can be used to optimize the treatment. This retrospective study aimed to assess the role of excision repair cross-complementing group-1 (ERCC1) and thymidylate synthase (TS) in tumors, and correlate expression levels and polymorphisms of these key determinants of drug activity with the outcome of MPM patients treated with carboplatin/pemetrexed in first-line setting.Analysis of TS and ERCC1 polymorphisms, mRNA and protein expression was done by PCR and immunohistochemistry [with the H-score (histologic score)] in tumor specimens from 126 MPM patients, including 99 carboplatin-/pemetrexed-treated patients.A significant correlation between low TS protein expression and disease control (DC) to carboplatin/pemetrexed therapy (P = 0.027), longer progression-free survival (PFS; P = 0.017), and longer overall survival (OS; P = 0.022) was found when patients were categorized according to median H-score. However, patients with the higher tertile of TS mRNA expression correlated with higher risk of developing progressive disease (P = 0.022), shorter PFS (P < 0.001), and shorter OS (P < 0.001). At multivariate analysis, the higher tertile of TS mRNA level and TS H-score confirmed their independent prognostic role for DC, PFS, and OS. No significant associations were found among ERCC1 protein expression, TS and ERCC1 polymorphisms, and clinical outcome.In our series of carboplatin-/pemetrexed-treated MPM patients, low TS protein and mRNA levels were significantly associated to DC, improved PFS, and OS. Prospective trials for the validation of the prognostic/predictive role of TS in MPM patients treated with pemetrexed-based regimens are warranted.
Parental pain is not associated with pain in the child: a population based study
Authors: G T Jones
Journal: Annals of the Rheumatic Diseases (2004)

Child pain is associated with adverse psychosocial factors. Some studies have shown an association between children's and parental pain. Children may "learn" pain behaviour from their parents.To examine whether an association exists between parent and child pain, and, if so, whether this relationship persists after adjusting for psychosocial difficulties in the child.1326 schoolchildren took part in a questionnaire based, cross sectional survey. Parents of study participants were sent a postal questionnaire. Occurrence of body pain was ascertained using blank body manikins and, in children, psychosocial factors were assessed using the Strengths and Difficulties Questionnaire. Three child-parent pain relationships were examined: any child pain with any parental pain or with parental widespread pain; and child low back pain with parental low back pain.The risk of child pain associated with parental reporting of pain was minor, and non-significant. Even when both parents reported widespread pain, the relative risk of pain in the child, after adjusting for age and psychosocial difficulties, was 1.2 (95% CI 0.5 to 3.2).Parental pain is not a risk for child pain. Pain behaviour is not learned. Rather, child pain is probably attributable to individual factors and the social environment.
Immediate and Long-Term Effect of Balloon Angioplasty or Stent Implantation on the Absolute and Relative Coronary Blood Flow Velocity Reserve
Authors: Rob A. M. van Liebergen, Jan J. Piek, Karel T. Koch, Robbert J. de Winter, Kong I. Lie
Journal: Circulation (1998)

Background —There is controversy regarding the immediate and long-term effects of PTCA on the coronary flow reserve. Methods and Results —A total of 54 patients with 1-vessel disease and normal left ventricular function were studied after balloon angioplasty (n=34) or stent implantation (n=20). Distal coronary blood flow velocity reserve (CFR) was defined as the ratio of adenosine-induced hyperemic versus baseline blood flow velocity with a 0.014-in Doppler guidewire. The relative CFR was defined as the ratio of the distal CFR and the reference CFR measured in the normal adjacent coronary artery. Hemodynamic and angiographic measurements were performed before and directly after balloon angioplasty or stent implantation and at 6-month follow-up. CFR after PTCA ≤2.5 was defined as an impaired CFR. Immediately after PTCA, CFR improved toward the range of the reference artery CFR. In both the balloon-treated and the stent-treated groups, initial high CFR values decreased and impaired CFR values increased at follow-up toward the values of the reference CFR in patients without restenosis. Impaired CFR after balloon angioplasty (33%) or stent implantation (58%) in patients without restenosis was related to an increased baseline flow velocity that normalized at follow-up. Patients with an increase of CFR after stenting were characterized by an unaltered baseline flow velocity and an increased adenosine-induced hyperemic flow velocity. Conclusions —An impaired CFR (≤2.5) is a frequent finding after balloon angioplasty or stent implantation as a result of a high baseline flow velocity. Normalization of impaired CFR at follow-up in patients without restenosis was associated with a decline of the baseline flow velocity after both balloon angioplasty and stent implantation, supporting the contention that this phenomenon relates to a slow recovery of autoregulation of the microvascular bed.
Strong Binding of Myosin Modulates Length-Dependent Ca <sup>2+</sup> Activation of Rat Ventricular Myocytes
Authors: Daniel P. Fitzsimons, Richard L. Moss
Journal: Circulation Research (1998)

Abstract —Reductions in sarcomere length (SL) and concomitant increases in interfilament lattice spacing have been shown to decrease the Ca 2+ sensitivity of tension in myocardium. We tested the idea that increased lattice spacing influences the SL dependence of isometric tension by reducing the probability of strong interactions of myosin crossbridges with actin, thereby decreasing cooperative activation of the thin filament. Single ventricular myocytes were isolated by enzymatic digestion of rat hearts and were subsequently rapidly skinned. Maximal tension and Ca 2+ sensitivity of tension (ie, pCa 50 ) were measured in the absence and presence of N -ethylmaleimide–modified myosin subfragment 1 (NEM-S1) at both short and long SLs. NEM-S1, a strong-binding non–tension-generating derivative of the myosin head, was applied to single skinned myocytes to cooperatively promote strong binding of endogenous myosin crossbridges. Compared with control myocytes at SL of ≈1.90 μm, application of NEM-S1 markedly increased submaximal Ca 2+ -activated tensions and thereby increased Ca 2+ sensitivity; ie, pCa 50 increased from 5.40±0.02 to 5.52±0.02 pCa units in the presence of NEM-S1. Furthermore, NEM-S1 treatment reversibly eliminated the SL dependence of the Ca 2+ sensitivity of tension, in that the ΔpCa 50 between short and long lengths was 0.02±0.01 pCa units in the presence of NEM-S1 compared with a ΔpCa 50 of 0.10±0.01 pCa units in control myocytes. From these results we conclude that the decrease in the Ca 2+ sensitivity of tension at short SL results predominantly from decreased cooperative activation of the thin filament due to reductions in the number of strong-binding crossbridges.
Increased risk of Alzheimer's disease in mothers of adults with Down's syndrome
Authors: N Schupf, D Kapell, J.H Lee, N Schupf, R Ottman, R Mayeux, Jh Lee, R Ottman, R Ottman, R Mayeux
Journal: The Lancet (1994)

Most adults with Down's syndrome (DS) develop neuropathology characteristic of Alzheimer's disease (AD) by the age of 40. Most of the non-dysjunction events in DS are of maternal origin. We postulated therefore that a shared genetic susceptibility to DS and AD would be associated with an increased frequency of AD among mothers, but not fathers, of individuals with DS. We further hypothesised that the shared susceptibility could involve an accelerated ageing process, leading to the birth of a child with DS to a relatively young mother and to an increased risk of dementia in the mother and her relatives. Families of 96 adults with DS and of 80 adults with other forms of mental retardation were ascertained through the New York State Developmental Disabilities services network. A semi-structured interview was used to obtain information on the presence or absence of non-stroke-related dementia and other disorders in parents. There was an increase in risk of dementia among mothers of DS probands compared with control mothers (risk ratio 2.6 [95% CI 0.9-7.3]). The risk of dementia among mothers who were 35 or younger when their DS children were born was 5 times that of control mothers (4.9 [1.6-15.4]). There was no increase in risk of dementia among mothers who were older (> 35 years) at the proband's birth (0.8 [0.2-3.4]). There was no difference in risk of dementia between fathers of DS cases and fathers of controls (1.2 [0.4-3.9]) and no discernible influence of age on this risk. Familial aggregation of dementia among mothers of adults with DS supports the hypothesis of a shared genetic susceptibility to DS and AD.
Arterial Puncture for Blood Gas Analysis
Authors: Shelly P Dev, Melinda D Hillmer, Mauricio Ferri
Journal: New England Journal of Medicine (2011)

This is a Video in Clinical Medicine from the New England Journal of Medicine. Arterial Puncture for Blood Gas Analysis Overview Radial arterial puncture for arterial blood gas analysis is a common procedure performed in medicine. It is a fundamental skill that all medical trainees need to acquire. This video will review radial arterial puncture in the adult population. Indications Puncture of the radial artery is the preferred method of obtaining an arterial blood sample for blood gas analysis. The chief indication for measurement of arterial blood gas level is to obtain values for the partial pressures of oxygen and carbon dioxide and for arterial pH. This information is needed when assessing a patient with acute, . . .
Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) αβ+CD8+ single-positive T cells, TCRγδ+ T cells, and natural killer–type cells in human thymus
Authors: Paola Romagnani, Francesco Annunziato, Elena Lazzeri, Lorenzo Cosmi, Chiara Beltrame, Laura Lasagni, Grazia Galli, Michela Francalanci, Roberto Manetti, Fabio Marra, Vittorio Vanini, Enrico Maggi, Sergio Romagnani
Journal: Blood (2001)
Putting the Clinical and Biological Heterogeneity of Non-Hodgkin Lymphoma into Context
Authors: Owen A. O'Connor, Kensei Tobinai
Journal: Clinical Cancer Research (2014)

The lymphomas represent one of the most heterogeneous groups of malignancies in all of cancer medicine. Whether one attempts to understand these diseases in the context of their complicated ontogeny, unique biologic features, or clinical presentation, this heterogeneity has been a mixed blessing. On the one hand, it has created an ever-changing way to classify these diseases, as classification schemes have been compelled to reflect the rapidly emerging information that seems to split the disease into smaller and smaller subtypes. On the other hand, the biologic and clinical dissection of these diseases has allowed for the identification of unique biologic features-features that have led to novel targets and generated a plethora of new drugs. Virtually every subtype of non-Hodgkin lymphoma has benefited from these efforts to understand the biology of the different subtypes. This paradigm has led to new clinical trials that tailor novel drug regimens to specific biologic disease subtypes. As a prelude to this CCR Focus section, we attempt to put this evolving heterogeneity into context, bridging historical and modern-day views of classification of these diseases. Then, some of the world's leading lymphoma researchers share their perspectives on how to formulate new concepts of care in this era of biologic discovery. Over a relatively short time, the advances in lymphoma research have been nothing short of stunning. There now seems to be little doubt that these recent breakthroughs will redound favorably on the majority of patients diagnosed with a lymphoproliferative malignancy. See all articles in this CCR Focus section, "Paradigm Shifts in Lymphoma."
The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission
Authors: Asami Tanimura, Maya Yamazaki, Yuki Hashimotodani, Motokazu Uchigashima, Shinya Kawata, Manabu Abe, Yoshihiro Kita, Kouichi Hashimoto, Takao Shimizu, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano
Journal: Neuron (2010)
Prevalence and Outcomes of Antimicrobial Treatment for Staphylococcus aureus Bacteremia in Outpatients with ESRD
Authors: Kevin E. Chan, H. Shaw Warren, Ravi I. Thadhani, David J.R. Steele, Jeffrey L. Hymes, Franklin W. Maddux, Raymond M. Hakim
Journal: Journal of the American Society of Nephrology (2012)

Staphylococcus bacteremia is a common and life-threatening medical emergency, but it is treatable with appropriate antibiotic therapy. To identify opportunities that may reduce morbidity and mortality associated with S. aureus, we analyzed data from 293,094 chronic hemodialysis outpatients to characterize practices of antibiotic selection. In the study population, the overall rate of bacteremia was 15.4 per 100 outpatient-years; the incidence rate for methicillin-sensitive (MSSA) was 2.1 per 100 outpatient-years, and the incidence rate for methicillin-resistant (MRSA) S. aureus was 1.9 per 100 outpatient-years. One week after the collection of the index blood culture, 56.1% of outpatients with MSSA bacteremia were receiving vancomycin, and 16.7% of outpatients with MSSA were receiving cefazolin. Among MSSA-bacteremic patients who did not die or get hospitalized 1 week after blood culture collection, use of cefazolin was associated with a 38% lower risk for hospitalization or death compared with vancomycin (adjusted HR=0.62, 95% CI=0.46–0.84). In conclusion, vancomycin is commonly used to treat MSSA bacteremia in outpatients receiving chronic dialysis, but there may be more risk of treatment failure than observed among those individuals who receive a β-lactam antibiotic such as cefazolin.
Contrasting Levels of Nucleotide Diversity on the Avian Z and W Sex Chromosomes
Authors: Hannah Montell, Anna-Karin Fridolfsson, Hans Ellegren
Journal: Molecular Biology and Evolution (2001)

Sex chromosomes may provide a context for studying the local effects of mutation rate on molecular evolution, since the two types of sex chromosomes are generally exposed to different mutational environments in male and female germ lines. Importantly, recent studies of some vertebrates have provided evidence for a higher mutation rate among males than among females. Thus, in birds, the Z chromosome, which spends two thirds of its time in the male germ line, is exposed to more mutations than the female-specific W chromosome. We show here that levels of nucleotide diversity are drastically higher on the avian Z chromosome than in paralogous sequences on the W chromosome. In fact, no intraspecific polymorphism whatsoever was seen in about 3.4 kb of CHD1W intron sequence from a total of >150 W chromosome copies of seven different bird species. In contrast, the amount of genetic variability in paralogous sequences on the Z chromosome was significant, with an average pairwise nucleotide diversity (ð) of 0.0020 between CHD1Z introns and with 37 segregating sites in a total of 3.8 kb of Z sequence. The contrasting levels of genetic variability on the avian sex chromosomes are thus in a direction predicted from a male-biased mutation rate. However, although a low gene number, as well as some other factors, argues against background selection and/or selective sweeps shaping the genetic variability of the avian W chromosome, we cannot completely exclude selection as a contributor to the low levels of variation on the W chromosome.
Early intervention in acute renal failure: Evidence of inadequate intravenous fluid treatment in UK hospitals
Authors: Nicholas J Matheson, Sarosh R Irani, Anushka Irani
Journal: BMJ (2006)

Evidence based diagnosis We may need to be open to new ideasEditor-If evidence based diagnosis is still in the dark ages, as Delamothe writes, 1 then so is evidence based treatment.The doctor's job is to choose the right treatment.If the diagnosis is wrong then the treatment will be wrong.Inaccurate diagnoses will also affect clinical trials.A treatment may be "evidence based" because it has worked in a published study, but some patients who would have responded might have been left out because of diagnostic inaccuracy while some patients with no prospect of responding might have been included incorrectly. 2vidence based diagnosis is about convincing others using shared rules of evidence that a diagnosis (and its implications in terms of treatment) should be accepted by others.Evidence is gathered from the individual and from groups of patients. 3Evidence based diagnosis means specifying the individual's facts in addition to pointing to facts relating to that diagnosis in the literature. 4ayes's theorem uses unconditional initial prior probabilities.Diagnostic leads are based on conditional probabilities and are used to initiate diagnostic thought processes. 4owever, closely related theorems can be used to interpret diagnostic leads, which allow doctors to reason with diagnostic evidence in a more familiar way, 3 thus reducing misunderstandings. 5So to improve evidence based diagnosis we also need to collect better data on diagnostic leads.The published evidence given for a diagnosis and any related actions cannot realistically be assembled when actually seeing a patient.A draft evidence based rationale might be prepared in advance.It would have to be capable of being accessed in seconds to provide evidence in support of a suspected diagnosis and decision arrived at by using kindness, imagination, and common sense.It could be put into context by inserting the patient's details into the draft evidence summoned up from a computer.If we are to make progress and allow evidence based diagnosis to emerge from the dark ages then in addition to doing more of the same, we may also have to be receptive to new ideas.
Muscle Ring Finger 1, but not Muscle Ring Finger 2, Regulates Cardiac Hypertrophy In Vivo
Authors: Monte S. Willis, Christopher Ike, Luge Li, Da-Zhi Wang, David J. Glass, Cam Patterson
Journal: Circulation Research (2007)

Muscle ring finger (MuRF) proteins have been implicated in transmitting mechanical forces to cell signaling pathways through their interactions with the giant protein titin. Recent evidence has linked mechanically-induced stimuli with the control of serum response factor activity and localization through MuRF2. This observation is particularly intriguing in the context of cardiac hypertrophy, where serum response factor transactivation is a key event necessary for the induction of cardiac hypertrophy in response to increased afterload. We have previously reported that MuRF1, which is also a titin-associated protein, exerts antihypertrophic activity in vitro. In the present study, we induced cardiac hypertrophy in mice lacking MuRF1 and MuRF2 to distinguish the physiologic role of these divergent proteins in vivo. We identified for the first time that MuRF1, but not MuRF2, plays a key role in regulating the induction of cardiac hypertrophy, likely by its direct interactions with serum response factor. These studies describe for the first time distinct and nonoverlapping functional characteristics of MuRF1 and MuRF2 in response to cardiac stress in vivo.