tbuckley/cabot-search huggingface dataset:
Effects of upper airway carbon dioxide on upper airway resistance and muscle activity in young guinea-pigs
Authors: A.K. Curran, K.D O'Halloran, A Bradford
Journal: European Respiratory Journal (2000)

The upper airway (UA) of adult animals is known to contain carbon dioxide-sensitive receptors and UA CO2 reflexly affects breathing, UA dilator muscle activity and UA resistance. These effects may function in the control of UA patency. There is evidence that some UA reflexes are stronger in young than in adult animals, but it is not known whether CO2-sensitive receptors are present in the UA of young animals, and the effects of UA CO2 on UA resistance and on UA dilator muscle activity have not been investigated in young animals. The responses of ventilation, UA resistance and geniohyoid muscle electromyographic activity to warm air containing 10% CO2 applied to the isolated UA were measured in anaesthetized, vagotomized young guinea-pigs breathing spontaneously through a low-cervical tracheostomy. Upper airway carbon dioxide caused an increase in ventilation (46.7+/-16.3 to 49.9+/-16.8 mL x min(-1) x 100 g body weight(-1)) and upper airway resistance (56.8+/-14.8 to 63.7+/-17.7 cmH2O x L(-1) x s(-1) x kg body weight(-1)). Similar effects were obtained following vagotomy. Geniohyoid activity became apparent following vagotomy and this activity was reduced by upper airway carbon dioxide. These responses were abolished by topical anaesthesia of the upper airway. This suggests that the reflexes seen are due to carbon dioxide-sensitive receptors in the upper airway.
Neutrophil ablation with anti-serum does not protect against phase 2 ventricular arrhythmias in anaesthetised rats with myocardial infarction
Authors: Hugh Clements-Jewery, David J. Hearse, Michael J. Curtis
Journal: Cardiovascular Research (2006)

Arrhythmias, including ventricular fibrillation (VF), occur in two phases after coronary obstruction, the first during the reversible stage of acute myocardial ischaemia (phase 1) and the second during evolution of the infarct (phase 2). We tested the hypothesis that phase 2 arrhythmias are mediated by actions of neutrophils accumulating within the infarct.Male rats (n=10 per group) were randomized to receive 2 ml/kg i.p. of either rabbit anti-rat neutrophil anti-serum or normal rabbit serum. After 17 h, single stage left coronary artery ligation was performed under pentobarbitone anaesthesia, and ischaemia was maintained for 240 min.Anti-serum pretreatment caused almost total neutropenia, reducing neutrophils in circulating blood from 2096+/-274x10(3) to 8+/-8x10(3) per ml (p<0.05). It also blocked neutrophil accumulation in the infarct, reducing cardiac myeloperoxidase activity from 74.7+/-27.4 to 9+/-3 mU per mg protein (p<0.05). Despite this, there was no significant difference between control and anti-serum-treated rats in the incidence of phase 2 VF (30% in each group) tachycardia (VT; 60% vs 80%) or number of ventricular premature beats (VPBs).Neutrophil accumulation within the evolving myocardial infarct does not mediate phase 2 VF.
A Physiological Approach to Aesthetic Preference – I. Paintings
Authors: M.A. de Jong
Journal: Psychotherapy and Psychosomatics (1972)

Ss were presented with 24 coloured projections of paintings that were selected by experts for their aesthetic value. During the presentations, recordings were made of heart rate (HR), respiration rate (RR) and skin conductance (SC). The scores on these measures were compared with the ratings by the Ss of the paintings on a rating scale that had at its extremes 'very beautiful' and 'very ugly'. Groups of Ss were recruited from three populations, each representing a different approach to art. The results indicated group differences for SC, a difference on RR for aesthetic preference and an interaction between group effect and aesthetic preference effect.
High human T cell lymphotropic virus type 1 (HTLV-1)-specific precursor cytotoxic T lymphocyte frequencies in patients with HTLV-1-associated neurological disease.
Authors: I Elovaara, S Koenig, A Y Brewah, R M Woods, T Lehky, S Jacobson
Journal: The Journal of Experimental Medicine (1993)

The frequencies of human T cell lymphotropic virus type 1 (HTLV-1)-specific CD8+ precursor cytotoxic T lymphocytes (pCTL) were quantitated from lymphocytes obtained from the peripheral blood and cerebrospinal fluid (CSF) of infected individuals with and without HTLV-1-associated neurological disease. An estimate of the pCTL was obtained by separating CD8+ cells, plating these cells in limiting dilution, and testing wells for HTLV-1 specific lysis. Targets consisted of autologous lymphoblastoid cell lines (LCL) infected with vaccinia constructs expressing HTLV-1 gene products or LCL pulsed with HTLV-1 synthetic peptides. In patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the frequency of HTLV-1 p40X-specific pCTL was at least 40-280-fold higher than in asymptomatic HTLV-1-infected individuals. All HAM/TSP patients (five of five) predominantly recognized HTLV-1 products encoded within the pX region. Lower pCTL to env were demonstrated in three patients, and only one of five HAM/TSP patients had pCTL to gag. A synthetic peptide corresponding to the tax region of HTLV-1 (peptide 11-19, amino acid sequence LLFGYPVYV) was recognized in association with human histocompatibility leukocyte antigen (HLA)-A2 in two HLA-A2 HAM/TSP patients with a high CD8+ pCTL frequency of 1/325 and 1/265, respectively. A second immunodominant region of HTLV-1 tax (peptide 90-55, amino acid sequence VPYKRIEEL) was identified to be restricted by HLA-B14 in two HLA-B14 HAM/TSP patients with a CD8+ pCTL frequency of 1/640 and 1/1,125, respectively. Lymphocytes from the CSF of a patient with HAM/TSP also showed a pCTL frequency against p40X of similar magnitude to that demonstrated from peripheral blood lymphocytes (PBL). The HLA-A2-mediated CSF pCTL activity to the immunodominant tax-specific peptide 11-19 was also comparable to pCTL from PBL. These results indicate that an extremely high pCTL frequency to HTLV-1 tax-encoded peptides may be related to pathogenesis of myeloneuropathy associated with HTLV-1.
Intraperitoneal Pretarget Radioimmunotherapy with CC49 Fusion Protein
Authors: Donald J. Buchsbaum, M.B. Khazaeli, Donald B. Axworthy, Jody Schultz, Tandra R. Chaudhuri, Kurt R. Zinn, Mark Carpenter, Albert F. LoBuglio
Journal: Clinical Cancer Research (2005)

This study examined a pretarget radioimmunotherapy strategy for treatment of an i.p. tumor model (LS174T).The strategy used regional administration (i.p.) of a novel targeting molecule composed of four CC49 anti-tumor-associated glycoprotein 72 (TAG-72) single-chain antibodies linked to streptavidin as a fusion protein (CC49 fusion protein); 24 hours later, a synthetic clearing agent was administered i.v. to produce hepatic clearance of unbound CC49 fusion protein/synthetic clearing agent complexes. Four hours later, a low molecular weight radiolabeled reagent composed of biotin conjugated to the chelating agent 7,10-tetra-azacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) complexed with (111)In-, (90)Y-, or (177)Lu-DOTA-biotin was injected.Radiolocalization to tumor sites was superior with i.p. administration of radiolabeled DOTA-biotin as compared with i.v. administration. Imaging and biodistribution studies showed excellent tumor localization of radioactivity with (111)In- or (177)Lu-DOTA-biotin. Tumor localization of (111)In-DOTA-biotin was 43% ID/g and 44% ID/g at 4 and 24 hours with the highest normal tissue localization in the kidney with 6% ID/g at 48 and 72 hours. Therapy studies with (90)Y-DOTA-biotin at doses of 400 to 600 microCi or (177)Lu-DOTA-biotin at doses of 600 to 800 microCi produced significant prolongation of survival compared with controls (P = 0.03 and P < 0.01).Pretarget radioimmunotherapy using regional administration of CC49 fusion protein and i.p. (90)Y- or (177)Lu-DOTA-biotin represents a successful therapeutic strategy in the LS174T i.p. tumor model and this strategy may be applicable to human trials in patients with i.p. ovarian cancer.
BCIRG 001 Molecular Analysis: Prognostic Factors in Node-Positive Breast Cancer Patients Receiving Adjuvant Chemotherapy
Authors: Charles Dumontet, Maryla Krajewska, Isabelle Treilleux, John R. Mackey, Miguel Martin, Mathieu Rupin, Laurence Lafanechère, John C. Reed
Journal: Clinical Cancer Research (2010)

There are currently no validated factors predictive of response to taxanes in patients with breast cancer. We analyzed specimens from patients included in the Breast Cancer International Research Group (BCIRG) 001 trial, a randomized study which showed the superiority of docetaxel/doxorubicin/cyclophosphamide over fluorouracil/doxorubicin/cyclophosphamide as adjuvant therapy for node-positive operable breast cancer in terms of disease-free survival (DFS) and overall survival (OS).Immunohistochemical assessment of biological markers included histologic grade, tumor size, estrogen and progesterone receptors, lymph node status, HER2, MUC1, Ki-67/MIB-1, p53, Bcl-2, Bax, Bcl-XL, BAG-1, beta-tubulin isotypes II, III and IV, tau protein, and detyrosinated alpha tubulin. Associations between selected parameters and survival were tested through univariate analyses, then completed with multivariate analyses and a bootstrap resampling technique.In univariate analysis histologic grade, tumor size, number of involved nodes, estrogen and progesterone receptor status, p53, Ki-67, tubulin III, and tau protein were associated both with DFS and with OS. In multivariate analysis estrogen and progesterone receptors, tumor size, number of involved nodes, and Ki-67 protein were associated both with DFS and with OS, whereas tau protein levels were correlated with DFS and tubulin III and P53 were correlated with OS. No interaction was observed between Ki-67 and treatment allocation.We conclude that the expression in primary tumors of Ki-67 and p53 protein, as well as of the microtubule-related parameters tau protein and tubulin III, are independent prognostic factors in patients receiving adjuvant chemotherapy for node-positive breast cancer but are not predictive of benefit from docetaxel-containing adjuvant chemotherapy.
Molecular Mechanisms of Fragile X Syndrome: A Twenty-Year Perspective
Authors: Michael R. Santoro, Steven M. Bray, Stephen T. Warren
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Fragile X syndrome (FXS) is a common form of inherited intellectual disability and is one of the leading known causes of autism. The mutation responsible for FXS is a large expansion of the trinucleotide CGG repeat in the 5' untranslated region of the X-linked gene FMR1. This expansion leads to DNA methylation of FMR1 and to transcriptional silencing, which results in the absence of the gene product, FMRP, a selective messenger RNA (mRNA)-binding protein that regulates the translation of a subset of dendritic mRNAs. FMRP is critical for mGluR (metabotropic glutamate receptor)-dependent long-term depression, as well as for other forms of synaptic plasticity; its absence causes excessive and persistent protein synthesis in postsynaptic dendrites and dysregulated synaptic function. Studies continue to refine our understanding of FMRP's role in synaptic plasticity and to uncover new functions of this protein, which have illuminated therapeutic approaches for FXS.
Septic shock – A contraindication for bridge to transplant?
Authors: Franziska Kaestner, Nicole Olewczynska, Ralf Kaiser, Philip Böhmer, Ingo Stehle, Katharina Rentz, Sven Henschke, Sebastian Fähndrich, Hans-Joachim Schäfers, Frank Langer, Heinrike Wilkens, Robert Bals, Philipp M. Lepper
Journal: European Respiratory Journal (2014)

Aim: To show first results of patients in septic shock being bridged to lung transplantation  (ltx) via extra corporal membrane oxygenation (ECMO).  Methods: A retrospective, single-center study observing septic patients in 2012 and 2013  taken on ECMO and being transplanted.  Results: 12 patients were included, 1 died on ECMO prior to ltx, 2 died in the first days  post transplantation. 7 were female; the mean age was 46. 5  patients suffered from mucoviscidosis, 3 had fibrosis, 2 COPD and another 2 PAH  respectively bronchiectasis. The mean time on the waiting list was 15.7 month, mean lung  allocation score 90 points. With 8 patients the sepsis was  classified as septic shock with the use of catecholamines. 5 patients had 4 SIRS  points, 4 had 3 and 2 had 2 points (one was connected to ECMO prior to the  transfer to our hospital). Mean time on ECMO was 35.5 days. Cannulation was in  all patients veno-venous and had to be changed in veno-(veno)-arterial in 3  patients. 8 patients did not need ECMO after ltx. The mean time on ICU after  ltx counted 44.5 days.  Conclusion: Infection and even more sepsis are commonly seen as at least relative  contraindications for taking patients on ECMO and bridging them to ltx. Main  reasons are the high mortality rate of septic patients on ECMO and the worse  outcomes after ltx. We were able to show that nearly all patients (11 from 12) could  be bridged to ltx and the overall mortality rate was relatively low (3 out of  12 died). There was no major correlation between high SIRS points, more ECMO  days or use of catecholamines and longer ICU stay or death. Further  consideration of the data is needed, in order to identify clues for best  outcomes in times of scarce resources.
HbA1c Diagnostic Categories and β-Cell Function Relative to Insulin Sensitivity in Overweight/Obese Adolescents
Authors: Lindsey A. Sjaarda, Sara F. Michaliszyn, SoJung Lee, Hala Tfayli, Fida Bacha, Lama Farchoukh, Silva A. Arslanian
Journal: Diabetes Care (2012)

OBJECTIVE The recommended HbA1c diagnostic categories remain controversial and their utility in doubt in pediatrics. We hypothesized that alterations in the pathophysiologic mechanisms of type 2 diabetes may be evident in the American Diabetes Association recommended at-risk/prediabetes category (HbA1c 5.7 to &amp;lt;6.5%). RESEARCH DESIGN AND METHODS We compared in vivo hepatic and peripheral insulin sensitivity by [6,6-2H2] glucose and a 3-h hyperinsulinemic-euglycemic clamp and β-cell function by a 2-h hyperglycemic clamp (∼225 mg/dL) in overweight/obese (BMI ≥85th percentile) adolescents with prediabetes (HbA1c 5.7 to &amp;lt;6.5%) (n = 160) to those with normal HbA1c (&amp;lt;5.7%) (n = 44). β-Cell function was expressed relative to insulin sensitivity (i.e., the disposition index = insulin sensitivity × first-phase insulin). RESULTS In the prediabetes versus normal HbA1c category, fasting glucose, insulin, and oral glucose tolerance test (OGTT) area under the curve for glucose and insulin were significantly higher; hepatic and peripheral insulin sensitivity were lower; and β-cell function relative to insulin sensitivity was lower (366 ± 48 vs. 524 ± 25 mg/kg/min; P = 0.005). A total of 27% of youth in the normal HbA1c category and 41% in the prediabetes HbA1c category had dysglycemia (impaired fasting glucose and/or impaired glucose tolerance) by a 2-h OGTT. CONCLUSIONS Overweight/obese adolescents with HbA1c in the at-risk/prediabetes category demonstrate impaired β-cell function relative to insulin sensitivity, a metabolic marker for heightened risk of type 2 diabetes. Thus, HbA1c may be a suitable screening tool in large-scale epidemiological observational and/or interventional studies examining the progression or reversal of type 2 diabetes risk.
Prenatal Diagnosis and Abortion for Congenital Abnormalities: Is It Ethical to Provide One Without the Other?
Authors: Angela Ballantyne, Ainsley Newson, Florencia Luna, Richard Ashcroft
Journal: The American Journal of Bioethics (2009)

This target article considers the ethical implications of providing prenatal diagnosis (PND) and antenatal screening services to detect fetal abnormalities in jurisdictions that prohibit abortion for these conditions. This unusual health policy context is common in the Latin American region. Congenital conditions are often untreated or under-treated in developing countries due to limited health resources, leading many women/couples to prefer termination of affected pregnancies. Three potential harms derive from the provision of PND in the absence of legal and safe abortion for these conditions: psychological distress, unjust distribution of burdens between socio-economic classes, and financial burdens for families and society. We present Iran as a comparative case study where recognition of these ethical issues has led to the liberalization of abortion laws for fetuses with thalassemia. We argue that physicians, geneticists and policymakers have an ethical and professional duty of care to advocate for change in order to ameliorate these harms.
Interferon-γ Induces AT <sub>2</sub> Receptor Expression in Fibroblasts by Jak/STAT Pathway and Interferon Regulatory Factor-1
Authors: Masatsugu Horiuchi, Wataru Hayashida, Masahiro Akishita, Seiichiro Yamada, Jukka Y. A. Lehtonen, Kouichi Tamura, Laurent Daviet, Yuquing E. Chen, Meiko Hamai, Tai-Xing Cui, Masaru Iwai, Yasuhiko Minokoshi
Journal: Circulation Research (2000)

The expression of angiotensin II type 2 (AT(2)) receptor is closely associated with cell growth, differentiation, and/or injury. We examined the effect of interferon (IFN)-gamma on AT(2) receptor expression in mouse fibroblast R3T3 cells and demonstrated that IFN-gamma treatment increased the expression of AT(2) receptor mRNA as well as its binding. Interferon regulatory factor (IRF)-1 was induced in mouse fibroblast R3T3 cells after IFN-gamma stimulation, and electrophoretic mobility shift assay showed an increase in IRF-1 binding with the IRF-specific binding sequence in the AT(2) receptor gene promoter region after IFN-gamma stimulation. The IRF-1 gene promoter contains an IFN-gamma-activated sequence (GAS) motif for possible binding of signal transducer(s) and activator(s) of transcription (STAT). Indeed, in R3T3 cells, IFN-gamma treatment resulted in rapid activation of Janus kinase (Jak) 1, Jak2, and STAT1 via tyrosine phosphorylation. Electrophoretic mobility shift assay with the GAS probe revealed increased STAT1 binding to the IRF-1 gene promoter in response to IFN-gamma stimulation. Transfection of GAS-binding oligonucleotides inhibited the effect of IFN-gamma on IRF-1 production, resulting in the AT(2) receptor trans-activation. Taken together, our data show that IFN-gamma upregulates AT(2) receptor expression in R3T3 cells via the activation of the intracellular Jak/STAT pathway and production of IRF-1.
Early Hospital Discharge Followed by Outpatient Management Versus Continued Hospitalization of Children With Cancer, Fever, and Neutropenia at Low Risk for Invasive Bacterial Infection
Authors: María E. Santolaya, Ana M. Alvarez, Carmen L. Avilés, Ana Becker, José Cofré, Miguel A. Cumsille, Miguel L. O'Ryan, Ernesto Payá, Carmen Salgado, Pamela Silva, Juan Tordecilla, Mónica Varas, Milena Villarroel, Tamara Viviani, Marcela Zubieta
Journal: Journal of Clinical Oncology (2004)

To compare outcome and cost of ambulatory versus hospitalized management among febrile neutropenic children at low risk for invasive bacterial infection (IBI).Children presenting with febrile neutropenia at six hospitals in Santiago, Chile, were categorized as high or low risk for IBI. Low-risk children were randomly assigned after 24 to 36 hours of hospitalization to receive ambulatory or hospitalized treatment and monitored until episode resolution. Outcome and cost were determined for each episode and compared between both groups using predefined definitions and questionnaires.A total of 161 (41%) of 390 febrile neutropenic episodes evaluated from June 2000 to February 2003 were classified as low risk, of which 149 were randomly assigned to ambulatory (n = 78) or hospital-based (n = 71) treatment. In both groups, mean age (ambulatory management, 55 months; hospital-based management, 66 months), sex, and type of cancer were similar. Outcome was favorable in 74 (95%) of 78 ambulatory-treated children and 67 (94%) of 71 hospital-treated children (P = NS). Mean cost of an episode was US 638 dollars (95% CI, 572 dollars to 703 dollars) and US 903 dollars (95% CI, 781 dollars to 1,025 dollars) for the ambulatory and hospital-based groups, respectively (P =.003).For children with febrile neutropenia at low risk for IBI, ambulatory management is safe and significantly cost saving compared with standard hospitalized therapy.
Noninvasive Prediction of Fracture Risk in Patients with Metastatic Cancer to the Spine
Authors: Brian D. Snyder, Marsha A. Cordio, Ara Nazarian, S. Daniel Kwak, David J. Chang, Vahid Entezari, David Zurakowski, Leroy M. Parker
Journal: Clinical Cancer Research (2009)

PURPOSE: Skeletal metastases affect up to 85% of breast cancer patients by the time of their death. This prospective in vivo study evaluated the diagnostic performance of computed tomography-based structural rigidity analysis (CTRA) to predict vertebral fracture risk in breast cancer patients with skeletal metastasis and in comparison with the current standard of care. EXPERIMENTAL DESIGN: Torso CT scans of 94 women with vertebral metastatic breast cancer were obtained as part of routine screening for lung and liver metastases. The load-bearing capacity (LBC) and axial (EA) and bending (EI) rigidities of vertebrae T8 to L5 were calculated from CT images. The LBC was normalized by patient body mass index (BMI) to account for height and mass variations. Vertebral fracture risk was also calculated using the current radiographic-based criteria based on lesion size and location. The actual occurrence of a new vertebral fracture was assessed radiographically over the ensuing 4 months. RESULTS: Eleven vertebral fractures occurred in 10 patients. The structural parameters EA, EI, LBC, and LBC/BMI were all 100% sensitive and 55%, 53%, 44%, and 70% specific to predict fracture risk, respectively. Although radiographic criteria correctly predicted all fracture cases (100% sensitive), only 48 of the 236 spinal segments that did not have a fracture were correctly predicted not to fracture (20% specific). CONCLUSIONS: CTRA, using CT scans as part of routine screening for lung and liver metastasis, is shown to be as sensitive as, and significantly more specific than, the current radiographic criteria for predicting vertebral fracture in breast cancer patients with skeletal metastasis. (Clin Cancer Res 2009;15(24):7676-83).