tbuckley/cabot-search huggingface dataset:
Mouse Mammary Tumor-Like Virus Is Associated with p53 Nuclear Accumulation and Progesterone Receptor Positivity but not Estrogen Positivity in Human Female Breast Cancer
Authors: Margaret Faedo, Caroline E. Ford, Reena Mehta, Katrina Blazek, William D. Rawlinson
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose is to compare the presence of proteins with known associations with breast cancer—progesterone receptor (PgR), estrogen receptor, and p53, with the prevalence of mouse mammary tumor virus (MMTV)-like DNA sequences in human female breast cancers. Experimental Design: A cohort of 128 Australian female breast cancers were screened for MMTV-like DNA sequences using PCR. The presence of PgR, estrogen receptor, and nuclear accumulation of p53 protein was assessed in the same samples using immunohistochemical staining. Results: Nuclear accumulation of p53 was significantly more prevalent (P = 0.05) in archival human breast cancers containing MMTV-like DNA sequences. The presence of progesterone receptor was significantly higher in MMTV-positive than MMTV-negative breast cancers (P = 0.01). No correlation between estrogen receptor and MMTV-like DNA sequences was found. Conclusions: MMTV causes breast cancer in mice, and hormones up-regulate expression of virus in mice mammary tissue. It is unknown if this is the case in human breast cancers shown to contain DNA of MMTV-like viruses. The positive association between MMTV-like DNA sequences and PgR indicates hormones and MMTV may play a role in human breast cancer. Mutations of the tumor suppressor gene p53 are common in human breast cancer and are associated with higher grades of cancer. The association of MMTV-like DNA sequences with higher grades of cancer, and the positive association between p53 and MMTV-like DNA sequences clearly warrant additional investigation.
MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort
Authors: Philip A. Beer, Peter J. Campbell, Linda M. Scott, Anthony J. Bench, Wendy N. Erber, David Bareford, Bridget S. Wilkins, John T. Reilly, Hans C. Hasselbalch, Richard Bowman, Keith Wheatley, Georgina Buck, Claire N. Harrison, Anthony R. Green
Journal: Blood (2008)
“I haven't even phoned my doctor yet.” The advice giving role of the pharmacist during consultations for medication review with patients aged 80 or more: qualitative discourse analysis
Authors: Charlotte Salter, Richard Holland, Ian Harvey, Karen Henwood
Journal: BMJ (2007)

<b>Objective</b> To explore the advice giving role of pharmacists during consultation for medication review with patients aged 80 or more. <b>Design</b> Discourse analysis. <b>Setting</b> Participants9 homes. <b>Participants</b> Subsample of consultations within a large randomised trial of home medication review among patients aged 80 or more who had been admitted to hospital. <b>Main outcome measures</b> Extent to which advice given by pharmacists was accepted and acknowledged by patients. <b>Results</b> Pharmacists found many opportunities to offer advice, information, and instruction. These advice giving modes were rarely initiated by the patients and were given despite a no problem response and deliberate displays of competence and knowledge by patients. Advice was often resisted or rejected and created interactional difficulties and awkward moments during the consultations. <b>Conclusions</b> The advice giving role of pharmacists during consultations with patients aged 80 or more has the potential to undermine and threaten the patients9 assumed competence, integrity, and self governance. Caution is needed in assuming that commonsense interventions necessarily lead to health gain.
Bronchoscopic or blind sampling techniques for the diagnosis of ventilator-associated pneumonia.
Authors: L Papazian, P Thomas, L Garbe, I Guignon, X Thirion, J Charrel, C Bollet, P Fuentes, F Gouin
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The purpose of this prospective postmortem study was to assess the diagnostic accuracy of bronchoscopic techniques (bronchoalveolar lavage [BAL] and protected specimen brush [PSB]) and nonbronchoscopic techniques (blind bronchial sampling [BBS] and mini-BAL) in the diagnosis of ventilator-associated pneumonia (VAP). The results of each technique were compared with histology and culture of lung tissue specimens obtained by surgical pneumonectomies in 38 patients who died after at least 72 h of mechanical ventilation. Histology was positive for VAP in 18 patients and negative in 20 patients. There were 12 definite VAP (positive histology and positive lung cultures) and 6 histologic VAP (positive histology and negative cultures). Clinical pulmonary infection score (CPIS) at a threshold of 6 achieved a sensitivity of 72% and a specificity of 85%. When the CPIS was combined with the logarithmic concentration of the predominant microorganism obtained from the BBS sample culture, specificity was increased to 95%, for a threshold of 10. Using 10(3) cfu/ml as the threshold of positivity for cultures obtained with PSB and mini-BAL samples and 10(4) cfu/ml for cultures obtained with BBS and BAL, the respective sensitivities of these techniques for definite VAP were 42, 67, 83, and 58%. The sensitivity of BBS was significantly higher than that of PSB (p < 0.05). The area under the receiver operator characteristic curve was significantly greater for BBS than PSB (p < 0.05). Given that it is more sensitive and noninvasive, BBS is preferable to PSB for the diagnosis of VAP.
Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012
Authors: L B Olafsdottir, H Erlendsdóttir, J Melo-Cristino, D M Weinberger, M Ramirez, K G Kristinsson, M Gottfredsson
Journal: Eurosurveillance (2014)

Epidemiology and clinical characteristics of invasive Group A streptococcal infections (IGASI) are highly variable. Long-term studies are needed to understand the interplay between epidemiology and virulence. In a population-based study of IGASI in Iceland from 1975 to 2012, 288 cases were identified by positive cultures from normally sterile body sites. Charts were reviewed retrospectively and emm-types of viable Streptococcus pyogenes isolates (n=226) determined. Comparing the first and last decade of the study period, IGASI incidence increased from 1.09 to 3.96 cases per 100,000 inhabitants per year. The most common were emm types 1 (25%), 28 (11%) and 89 (11%); emm1 strains were most likely to cause severe infections. Infections in adults were significantly more likely to be severe during the seasonal peak from January to April (risk ratio: 2.36, 95% confidence interval: 1.34–4.15). Significant seasonal variability in severity was noted among patients with diagnosis of sepsis, respiratory infection and cellulitis, with 38% of severe infections in January to April compared with 16% in other months (p<0.01). A seasonal increase in severity of IGASI suggested that generalised seasonal increase in host susceptibility, rather than introduction of more virulent strains may play a role in the pathogenesis of these potentially fatal infections.
Physiological effects of posture on mask ventilation in awake stable chronic hypercapnic COPD patients
Authors: R. Porta, M. Vitacca, E Clini, N Ambrosino
Journal: European Respiratory Journal (1999)

Stable chronic hypercapnic patients are often prescribed long-term mask noninvasive pressure support ventilation (NPSV). There is a lack of information on the effects of posture on NPSV. Therefore posture induced changes in physiological effects of NPSV in awake stable chronic hypercapnic patients were evaluated. In 12 awake chronic obstructive pulmonary disease (COPD) patients breathing pattern, respiratory muscles, mechanics and dyspnoea (by visual analogue scale: VAS) were evaluated during spontaneous breathing (SB) in sitting posture and during NPSV in sitting, supine and lateral positions randomly assigned. Arterial blood gases were evaluated during SB and at the end of the last NPSV session (whatever the posture). As expected NPSV resulted in a significant improvement in carbon dioxide tension in arterial blood (Pa,CO2) (from 7.4+/-0.85 to 6.9+/-0.7 kPa). When compared with SB, sitting NPSV resulted in a significant increase in tidal volume and minute ventilation and in a significant decrease in breathing frequency. Inspiratory muscle effort as assessed by oesophageal pressure swings and pressure-time product per minute (from 14+/-4.8 to 6.2+/-3.5 cmH2O, and from 240+/-81 to 96+/-60 cmH2O x s x min(-1) respectively), intrinsic dynamic positive end expiratory pressure (from 2.7+/-2.3 to 1.4+/-1.3 cmH2O) and expiratory airway resistance (from 18+/-7 to 5+/-3 cmH2O x L x s(-1)) decreased during sitting NPSV, whereas VAS did not change. Changing posture did not significantly affect any parameter independently of the patients weight, whether obese or not. In awake stable hypercapnic chronic obstructive pulmonary disease patients changing posture does not significantly influence breathing pattern and respiratory muscles during noninvasive pressure support ventilation suggesting that mask ventilation may be performed in different positions without any relevant difference in its effectiveness.
The relation between spirometric measurements and arterial blood gas analysis in patients with chronic airflow obstruction
Authors: E. M. Shibel, K. M. Moser
Journal: Thorax (1970)

Spirometric studies and arterial blood gas analyses were statistically evaluated in 75 patients with chronic airways obstruction to determine whether any spirometric parameters can predict arterial blood gas status. Radioactive lung scans, both ventilation (using <sup>133</sup>Xe gas) and perfusion (using <sup>131</sup>I-MAA), were performed in selected patients. In all 75 patients as one group, no spirometric parameter correlated with resting arterial blood gases. Comparing spirometric values with arterial blood studies during exercise, 5% carbon dioxide breathing and 100% oxygen breathing revealed no consistently predictive correlation coefficients. Ventilation and perfusion lung scanning revealed that in patients whose ventilation/perfusion (V̇/Q) `match9 was good, arterial blood gases approached normal, while hypoxaemia and/or hypercapnia were present when V̇/Q relationships were disturbed. Spirometry measures static and dynamic lung volumes, reflecting the mechanical and structural status of the lung-bellows system. Arterial blood gas status is conditioned by severe factors, including V̇/Q relationship, and can be determined accurately only by measurement in each individual patient.
Endothelial Dysfunction and Hypertension in Rats Transduced With CYP4A2 Adenovirus
Authors: Ji-Shi Wang, Harpreet Singh, Frank Zhang, Tsuneo Ishizuka, Huan Deng, Rowena Kemp, Michael S. Wolin, Thomas H. Hintze, Nader G. Abraham, Alberto Nasjletti, Michal Laniado-Schwartzman
Journal: Circulation Research (2006)

Vascular cytochrome P450 (CYP) 4A enzymes catalyze the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid which participates in the regulation of vascular tone by sensitizing the smooth muscle cells to constrictor and myogenic stimuli. This study was undertaken to investigate the consequences of CYP4A overexpression on blood pressure and endothelial function in rats treated with adenoviral vectors carrying the CYP4A2 construct. Intravenous injection of Adv-CYP4A2 increased blood pressure (from 114+/-1 to 133+/-1 mm Hg, P<0.001), and interlobar renal arteries from these rats displayed decreased relaxing responsiveness to acetylcholine, which was offset by treatment with an inhibitor of CYP4A. Relative to data in control rats, arteries from Adv-CYP4A2-transduced rats produced more 20-HETE (129+/-10 versus 97+/-7 pmol/mg protein, P<0.01) and less nitric oxide (NO; 4.2+/-1.6 versus 8.4+/-1 nmol nitrite+nitrate/mg; P<0.05). They also displayed higher levels of oxidative stress as measured by increased generation of superoxide anion and increased expression of nitrotyrosine and gp91phox. Collectively, these findings demonstrate that augmentation in vascular 20-HETE promotes the development of hypertension and causes endothelial dysfunction, a condition characterized by decreased NO synthesis and/or bioavailability, imbalance in the relative contribution of endothelium-derived relaxing and contracting factors, and enhanced endothelial activation.
Purification and fine characterization of a major allergen from <i>Olea europaea</i> pollen extract
Authors: F. De Cesare, C. Pini, G. Di Felice, M. F. Caiaffa, L. Macchia, A. Tursi, R. Tinghino, S. Palumbo, F. Sallusto, R. Federico
Journal: Allergy (1993)

Olea europaea (olive) pollen extract was prepared by aqueous extraction and characterized by biochemical and immunochemical methods. Two components, displaying respective mol. wt. of 17,000 and 19,000, were the most reactive allergens, being the doublet (designated Ole e I) recognized by most sera tested. The 19,000 mol. wt. component, purified by conventional biochemical procedure and lectin-affinity chromatography from the Ole e I doublet, was deglycosylated and analyzed by SDS-PAGE and by ELISA inhibition. The results obtained suggest that the 19,000 mol. wt. component represents the glycosylated form of the 17,000 component.
Crohn's disease involving the penis.
Authors: G Slaney, S Muller, J Clay, A H Sumathipala, P Hillenbrand, H Thompson
Journal: Gut (1986)

Perianal complications of Crohn's disease occur in 25-70% of patients but perineal and genital lesions are rare. Treatment is controversial and there is a risk of recurrent or persistent disease. We report two cases of Crohn's disease involving the penis, one with multiple scrotal urinary fistulae, partial destruction of the proximal urethra, and ulceration of the penile shaft; the other with metastatic cutaneous ulceration of the penile shaft. The second case is particularly unusual in that the patient presented at the VD clinic as a case of syphilis.
Insulinoma in a Patient With NIDDM
Authors: L A Kane, C S Grant, T B Nippoldt, F J Service
Journal: Diabetes Care (1993)

Objective— To confirm insulinoma as the cause of hypoglycemia in a patient with NIDDM and determine the frequency of the co-occurrence of these two conditions. Research Design and Methods— The patient underwent an in-hospital prolonged fast (≤72 h), according to standard protocol, and an ultrasound examination of the pancreas. All cases of histologically confirmed insulinoma at this institution over the period of 1927–1992 were reviewed to determine the prevalence of pre-existent diabetes mellitus. Results— After 10 h of fasting, plasma glucose was low (1.89 mM); plasma insulin (258 pM) and C-peptide (1.39 nM) were elevated in the absence of sulfonylurea in the plasma. An insulinoma detected by ultrasonography was removed surgically with subsequent reoccurrence of insulin-requiring diabetes. Among 313 cases of insulinoma confirmed at this institution, this patient is the only one with pre-existent diabetes mellitus. Conclusions— Insulinoma occurs extraordinarily rarely in patients with pre-existing NIDDM.
THE BIONOMICS OF THE MALTESE PHLEBOTOMI
Authors: P. J. Marett
Journal: BMJ (1915)

ZIA J_IWLTU Y3 are found here it is at least as likely that they may be a factor in the causation of this seven-day tvpe of fever, as they appsar to be iiow generally regarded as being the active agents in its propagation in other parts of the country.
Mouse Models of Human Cancer
Authors: Barbara C. Böck, Ulrike Stein, Clemens A. Schmitt, Hellmut G. Augustin
Journal: Cancer Research (2014)

The Helmholtz Alliance Preclinical Comprehensive Cancer Center (PCCC; www.helmholtz-pccc.de) hosted the "1st International Kloster Seeon Meeting on Mouse Models of Human Cancer" in the Seeon monastery (Germany) from March 8 to 11, 2014. The meeting focused on the development and application of novel mouse models in tumor research and high-throughput technologies to overcome one of the most critical bottlenecks in translational bench-to-bedside tumor biology research. Moreover, the participants discussed basic molecular mechanisms underlying tumor initiation, progression, metastasis, and therapy resistance, which are the prerequisite for the development of novel treatment strategies and clinical applications in cancer therapy.
Molecular Pathways: Targeting MYC-induced Metabolic Reprogramming and Oncogenic Stress in Cancer
Authors: Bo Li, M. Celeste Simon
Journal: Clinical Cancer Research (2013)

MYC is a multifunctional transcription factor that is deregulated in many human cancers. MYC impacts a collaborative genetic program that orchestrates cell proliferation, metabolism, and stress responses. Although the progression of MYC-amplified tumors shows robust dependence on MYC activity, directly targeting MYC as a therapeutic method has proven to be technically difficult. Therefore, alternative approaches are currently under development with a focus on interference with MYC-mediated downstream effects. To fuel rapid cell growth, MYC reprograms cancer cell metabolism in a way that is substantially different from normal cells. The MYC-induced metabolic signature is characterized by enhanced glucose and glutamine uptake, increased lactate production, and altered amino acid metabolism. Targeting MYC-reprogrammed cancer cell metabolism is considered to be promising based on multiple preclinical studies. In addition, the increased biosynthetic demand of MYC-driven tumors coupled with limited nutrient access within tumor microenvironments create multiple levels of oncogenic stress, which can also be used as tumor-specific targets for pharmacologic intervention. Presumably, the best therapeutic strategy for treating MYC-amplified tumors is combined targeting of multiple MYC-mediated pathways, especially those involved in regulating cell proliferation, metabolism, and oncogenic stress.
Serotonin Neuron Loss and Nonmotor Symptoms Continue in Parkinson’s Patients Treated with Dopamine Grafts
Authors: Marios Politis, Kit Wu, Clare Loane, Niall P. Quinn, David J. Brooks, Wolfgang H. Oertel, Anders Björklund, Olle Lindvall, Paola Piccini
Journal: Science Translational Medicine (2012)

Dopamine-rich fetal tissue grafts relieve motor but not nonmotor symptoms in PD patients, requiring additional therapeutic interventions to treat continuing serotonergic denervation.
Polypharmacy and Medication Adherence in Patients With Type 2 Diabetes
Authors: Richard W. Grant, Nicole G. Devita, Daniel E. Singer, James B. Meigs
Journal: Diabetes Care (2003)

OBJECTIVE—To determine medication adherence and predictors of suboptimal adherence in a community cohort of patients with diabetes and to test the hypothesis that adherence decreases with increased number of medicines prescribed. RESEARCH DESIGN AND METHODS—A total of 128 randomly selected patients with type 2 diabetes from a single community health center responded to a pharmacist-administered questionnaire regarding medication use. Survey data were linked to clinical data available from the electronic medical record. We assessed self-reported adherence rates for each diabetes-related medicine, barriers and attitudes regarding medication use, and HbA1c, total cholesterol, and blood pressure levels. RESULTS—Patients were taking a mean of 4.1 (±1.9) diabetes-related medicines. The average 7-day adherence was 6.7 ± 1.1 days. Total number of medicines prescribed was not correlated with medication adherence. Adherence was significantly lower for medicines not felt to be improving current or future health (6.1 vs. 6.9 days out of 7, P &amp;lt; 0.001). Among patients on three or more medicines, 71% (15 of 21 patients) with suboptimal adherence were perfectly adherent with all but one medicine. Side effects were the most commonly reported problem with medication use. Of 29 medicines causing side effects that interfered with adherence, 24 (83%) did so for &amp;gt;1 month, and only 7 (24%) were reported to the patient’s primary care physician. CONCLUSIONS—In this sample, patients reported very high medication adherence rates regardless of number of medicines prescribed. Among patients on multiple medicines, most patients with suboptimal adherence were perfectly adherent to all but one medicine. Unreported side effects and a lack of confidence in immediate or future benefits were significant predictors of suboptimal adherence. Physicians should not feel deterred from prescribing multiple agents in order to achieve adequate control of hyperglycemia, hypertension, and hyperlipidemia.
Effect of Changes in Salt Intake on Arterial Pressure and Renal Function in Partially Nephrectomized Dogs
Authors: JIMMY B. LANGSTAN, ARTHUR C. GUYTOM, B. H. DOUGLAS, P. E. DORSETT, Ann Russel, R. E. McCaa
Journal: Circulation Research (1963)

Approximately 70% of the total renal tissue was removed in 11 dogs. Control values were then established for mean arterial pressure, urine and plasma sodium concentrations, blood urea nitrogen, glomerular filtration rate, total body weight, and rate of urine formation for these dogs and for two dogs whose kidneys were left intact. Two of the partially nephrectomized dogs were allowed to drink water for the duration of the study while the other animals were required to drink 0.9% sodium chloride solution for various periods of time. The increased salt intake resulted in a 30% to 40% increase in arterial pressure within 48 to 72 hours; plasma sodium concentration increased concomitantly with the development of hypertension. The elevated pressure could be reduced to normal levels within 24 hours by simply allowing the dogs to drink tap water again. Similar results were obtained in a single dog in which renal function had fortuitously been reduced by chronic pyelonephritis.
Cytotoxicity and Proteomics Analyses of OSU03013 in Lung Cancer
Authors: Yi-Hung Tan, Kung-Hsueh Lee, Topp Lin, Ying-Chieh Sun, Hsiu Mei Hsieh-Li, Hsueh-Fen Juan, Yi-Ching Wang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Most lung cancer patients have some resistance to and suffer from side effects of conventional chemotherapy. Thus, identification of a novel anticancer drug with better target selectivity for lung cancer treatment is urgently needed. Experimental Design: In order to investigate whether OSU03013, a derivative of celecoxib, can be a potential drug for lung cancer treatment, we examined its cytotoxicity mechanisms by flow cytometry and phosphatidylserine staining in A549, CL1-1, and H1435 lung cancer cell lines, which are resistant to the conventional drug, cisplatin. In addition, we identified the affected proteins by proteomics and confirmed the selected proteins by Western blot analysis. We examined the interaction between OSU03013 and potential target protein by molecular modeling. Results: Our results indicated that OSU03013 had low-dose (1∼4 μM) cytotoxicity in all lung cancer cell lines tested 48 hours posttreatment. OSU03013 caused cell cycle G1 phase arrest and showed phosphatidylserine early apoptosis via endoplasmic reticulum stress. Several proteins such as heat shock protein 27, 70, and 90, CDC2, α-tubulin, annexin A3, cAMP-dependent protein kinase, glycogen synthase kinase 3-beta, and β-catenin were identified by proteomics and confirmed by Western blot. In addition, molecular modeling showed that OSU03013 competes with ATP to bind to cAMP-dependent protein kinase. Conclusions: We identified for the first time that OSU03013 inhibits cAMP-dependent protein kinase activity and causes dephosphorylation of glycogen synthase kinase 3-beta leading to β-catenin degradation, which is often overexpressed in lung cancer. Our molecular and proteomic results show the potential of OSU03013 as an anticancer drug for lung cancer.