tbuckley/cabot-search huggingface dataset:
Torulopsis glabrata Endocarditis
Authors: H. Douglas Holliday
Journal: JAMA (1980)

<i>TORULOPSIS glabrata</i>is a fungal organism of the family Cryptococcaceae with low pathogenicity for man. It is a frequent saprophyte and can be cultured from the stool, skin, mouth, and vagina in healthy persons. Infections due to<i>T glabrata</i>occur principally in patients whose immune systems are suppressed, have indwelling venous or urinary catheters, or have been treated with broad-spectrum antibiotics.<sup>1</sup>Documented cases of endocarditis due to<i>T glabrata</i>are uncommon; predisposing causes and clinical features have not been reviewed. A patient had tricuspid valve endocarditis secondary to<i>T glabrata</i>. Her illness followed abdominal surgery and was characterized by 33 months of episodic chills and fever. Other patients with<i>T glabrata</i>endocarditis have been described with features remarkably similar to those of our patient.<sup>2,3</sup>These similarities prompted this case report and review of the literature. <h3>Report of a Case</h3> A 63-year-old diabetic woman had undergone a uretero-ureterostomy for
Podoplanin-Positive Cancer-Associated Fibroblasts in the Tumor Microenvironment Induce Primary Resistance to EGFR-TKIs in Lung Adenocarcinoma with EGFR Mutation
Authors: Tatsuya Yoshida, Genichiro Ishii, Koichi Goto, Shinya Neri, Hiroko Hashimoto, Kiyotaka Yoh, Seiji Niho, Shigeki Umemura, Shingo Matsumoto, Hironobu Ohmatsu, Shinsuke Iida, Akio Niimi, Kanji Nagai, Yuichiro Ohe, Atsushi Ochiai
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The biologic characteristics of microenvironmental constituents, especially cancer-associated fibroblasts (CAF), can be key regulators of the cellular sensitivity to molecular-targeted therapy. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have marked therapeutic effects against non–small cell lung cancer (NSCLC) with EGFR mutations, but some patients have exhibited primary resistance to EGFR-TKIs. We recently reported that podoplanin-positive fibroblasts are associated with a tumor-promoting phenotype of CAFs in lung adenocarcinoma. The aim of this study was to evaluate whether the susceptibility of NSCLC to EGFR-TKIs could be affected by podoplanin-expressing CAFs. Experimental Design: We evaluated the EGFR-TKI sensitivity of EGFR-mutant lung adenocarcinoma cell lines cocultured with podoplanin-expressing CAFs. We also examined the association between the expression of podoplanin in CAFs in surgical specimens and EGFR-TKI response of postoperative recurrent patients with EGFR mutations (N = 106). Results: Lung adenocarcinoma cell lines became more resistant to EGFR-TKI when cocultured with podoplanin-expressing CAFs, compared with control CAFs in vitro. The knockdown of podoplanin expression on CAFs cancelled the resistance to EGFR-TKIs in cancer cells. Compared with control CAFs, the cancer cells that were cocultured with podoplanin-positive CAFs continued to exhibit significantly higher p-ERK levels after treatment with gefitinib. Furthermore, postoperative recurrent patients with podoplanin-positive CAFs had a significantly lower overall response rate to EGFR-TKIs compared with those with podoplanin-negative CAFs (53% vs. 83%; P &amp;lt; 0.01). Conclusions: Podoplanin-positive CAFs play an important role in primary resistance to EGFR-TKIs and may be an ideal therapeutic target for use in combination therapy with EGFR-TKIs. Clin Cancer Res; 21(3); 642–51. ©2014 AACR.
Hospital Ship Psychiatry in a War Zone
Authors: ROBERT E. STRANGE, RANSOM J. ARTHUR
Journal: American Journal of Psychiatry (1967)

The hospital ship Repose has provided combat-supportive medical services for U. S. forces in Viet Nam, receiving casualties evacuated directly from the field medical units as well as patients referred from the major hospitals ashore. Although the psychiatric patient population aboard was similar in many respects to that at any other military hospital, the function of the ship as an intermediate echelon of psychiatric treatment in the war zone helped to maintain a strong back-to-duty orientation, and 50 percent of all psychiatric patients taken aboard were returned to full duty.
Intersections between Pulmonary Development and Disease
Authors: Jeffrey A. Whitsett, Hans Michael Haitchi, Yutaka Maeda
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Recent advances in cellular, molecular, and developmental biology have revolutionized our concepts regarding the process of organogenesis that have important implications for our understanding of both lung formation and pulmonary disease pathogenesis. Pulmonary investigators have long debated whether developmental processes are recapitulated during normal repair of the lung or in the setting of chronic pulmonary diseases. Although the cellular events involved in lung morphogenesis and those causing pulmonary disease are likely to include processes that are distinct, there is increasing evidence that the pathogenesis of many lung disorders involves the same genetic machinery that regulates cell growth,specification, and differentiation during normal lung development.
Reactivity of a monoclonal antibody with human ovarian carcinoma.
Authors: R C Bast, M Feeney, H Lazarus, L M Nadler, R B Colvin, R C Knapp
Journal: Journal of Clinical Investigation (1981)

A murine monoclonal antibody (OC125) has been developed that reacts with each of six epithelial ovarian carcinoma cell lines and with cryopreserved tumor tissue from 12 of 20 ovarian cancer patients. By contrast, the antibody does not bind to a variety of nonmalignant tissues, including adult and fetal ovary. OC125 reacts with only 1 of 14 cell lines derived from nonovarian neoplasms and has failed to react with cryostat sections from 12 nonovarian carcinomas.
Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis
Authors: Harry Roger Buller, Claudette Bethune, Sanjay Bhanot, David Gailani, Brett P. Monia, Gary E. Raskob, Annelise Segers, Peter Verhamme, Jeffrey I. Weitz
Journal: New England Journal of Medicine (2014)

Experimental data indicate that reducing factor XI levels attenuates thrombosis without causing bleeding, but the role of factor XI in the prevention of postoperative venous thrombosis in humans is unknown. FXI-ASO (ISIS 416858) is a second-generation antisense oligonucleotide that specifically reduces factor XI levels. We compared the efficacy and safety of FXI-ASO with those of enoxaparin in patients undergoing total knee arthroplasty.In this open-label, parallel-group study, we randomly assigned 300 patients who were undergoing elective primary unilateral total knee arthroplasty to receive one of two doses of FXI-ASO (200 mg or 300 mg) or 40 mg of enoxaparin once daily. The primary efficacy outcome was the incidence of venous thromboembolism (assessed by mandatory bilateral venography or report of symptomatic events). The principal safety outcome was major or clinically relevant nonmajor bleeding.Around the time of surgery, the mean (±SE) factor XI levels were 0.38±0.01 units per milliliter in the 200-mg FXI-ASO group, 0.20±0.01 units per milliliter in the 300-mg FXI-ASO group, and 0.93±0.02 units per milliliter in the enoxaparin group. The primary efficacy outcome occurred in 36 of 134 patients (27%) who received the 200-mg dose of FXI-ASO and in 3 of 71 patients (4%) who received the 300-mg dose of FXI-ASO, as compared with 21 of 69 patients (30%) who received enoxaparin. The 200-mg regimen was noninferior, and the 300-mg regimen was superior, to enoxaparin (P<0.001). Bleeding occurred in 3%, 3%, and 8% of the patients in the three study groups, respectively.This study showed that factor XI contributes to postoperative venous thromboembolism; reducing factor XI levels in patients undergoing elective primary unilateral total knee arthroplasty was an effective method for its prevention and appeared to be safe with respect to the risk of bleeding. (Funded by Isis Pharmaceuticals; FXI-ASO TKA ClinicalTrials.gov number, NCT01713361.).
Dose-finding and 24-h monitoring for efficacy and safety of aerosolized Nacystelyn in cystic fibrosis
Authors: E.M. App, D. Baran, I. Dab, A. Malfroot, M. Coffiner, F. Vanderbist, M. King
Journal: European Respiratory Journal (2002)

The aim of the present studies was to investigate the tolerability and activity of a novel mucolytic drug, Nacystelyn (NAL), for the treatment of cystic fibrosis (CF) lung disease. In study 1, involving 10 CF patients, the main objective was to determine the tolerability and potential efficacy of a range of single doses of NAL in comparison to a placebo, in order to establish an optimal dose for further testing. On five consecutive scheduled treatment days, patients inhaled either from two (4 mg) to eight puffs (16 mg) of a single dose of NAL from the range, administered in an open-label fashion, or 12 puffs of active NAL (24 mg) versus 12 puffs of placebo, administered in a randomized double-blind fashion. Pulmonary function data were unaffected and clinically-adverse effects were limited to wheezing in some patients that inhaled 12 puffs of either placebo or active drug. Subsequent rheological analysis of their sputum showed a dose-dependent decrease in sputum viscoelasticity, accompanied by a decrease in sputum solids content and an increase in chloride and sodium concentrations. In study 2, involving 12 CF patients, the clinical safety and mucolytic activity of a single dose of NAL was monitored over 24 h. On different scheduled treatment days, 7 days apart, patients inhaled a single dose of 12 puffs of active NAL (24 mg) or 12 puffs of placebo drug in a randomized, double-blind sequence, with sputum samples taken at intervals before and after inhalation. Mucus rigidity decreased following NAL inhalation, with the maximum effect observed at 4 h; the 1-, 2- and 4-h NAL rheology results were significantly different from placebo. No adverse effects were observed. The drug was well tolerated in both studies. Sputum results were predictive of improved clearability by ciliary and cough transport mechanisms.
Tumour necrosis factor blockade mediates altered serotonin transporter availability in rheumatoid arthritis: a clinical, proof-of-concept study
Authors: Jonathan Cavanagh, Carolyn Paterson, John McLean, Sally Pimlott, Moira McDonald, James Patterson, David Wyper, Iain McInnes
Journal: Annals of the Rheumatic Diseases (2010)

Depression in those who are ill is 5–10 times more common than in the general population. Increasing evidence implicates bidirectional biological mechanisms linking mood disorders and medical conditions.1 Depressive symptoms are significantly more common in rheumatoid arthritis (RA) than in the general population. Conservative estimates suggest major depressive disorder in between 13% and 17% of patients with RA. However, prevalence exceeding 40% has been reported in a recent study, with up to 11% of patients experiencing suicidal ideation.1 Major depressive disorder is an independent risk factor for both work disability and mortality in patients with RA.2

Cytokine dysregulation is central to the pathogenesis of RA with functional implications for breach of tolerance and autoimmunity, subsequent inflammation and articular dysfunction.3 Tumour necrosis factor (TNF), in particular, appears to be of pivotal importance in pathogenesis, based …
Problems of bacterial infection in patients with liver disease.
Authors: R J Wyke
Journal: Gut (1987)

<h3>Abstract</h3> ER stress is implicated in many chronic diseases, but very little is known about how the unfolded protein response (UPR) responds to persistent ER stress <i>in vivo</i>. Here, we experimentally reconstituted chronic ER stress in the mouse liver, using repeated injection of a low dose of the ER stressor tunicamycin. Paradoxically, this treatment led to feedback-mediated suppression of a select group of mRNAs, including those encoding the ER chaperones BiP and GRP94. This suppression was due to both silencing of the ATF6a pathway of UPR-dependent transcription and enhancement of mRNA degradation, most likely via regulated IRE1-dependent decay (RIDD). The suppression of <i>Bip</i> mRNA was phenocopied by ectopic overexpression of BiP protein, and was also observed in obese mice. Our findings suggest that persistent cycles of UPR activation and deactivation create an altered, quasi-stable setpoint for UPR-dependent transcriptional regulation—an outcome that could be relevant to conditions such as metabolic syndrome.
The prevalence of rhinitis and its association with smoking and obesity in a nationwide survey of <scp>J</scp>apanese adults
Authors: S. Konno, N. Hizawa, Y. Fukutomi, M. Taniguchi, Y. Kawagishi, C. Okada, Y. Tanimoto, K. Takahashi, A. Akasawa, K. Akiyama, M. Nishimura
Journal: Allergy (2012)

Abstract Background Rhinitis is a common disease, and its prevalence is increasing worldwide. Several studies have provided evidence of a strong association between asthma and rhinitis. Although smoking and obesity have been extensively analyzed as risk factors of asthma, associations with rhinitis are less clear. Objective The aims of our study were (i) to evaluate the prevalence of rhinitis using the E uropean C ommunity R espiratory H ealth S urvey ( ECRHS ) questionnaire in J apanese adults and (ii) to evaluate the associations of smoking and body mass index ( BMI ) with rhinitis. Methods Following our study conducted in 2006–2007 to determine the prevalence of asthma using the ECRHS questionnaire, our present analysis evaluates the prevalence of rhinitis and its association with smoking and BMI in J apanese adults 20–79 years of age ( N = 22819). We classified the subjects (20–44 or 45–79 years) into four groups as having (i) neither rhinitis nor asthma; (ii) rhinitis without asthma; (iii) asthma without rhinitis; or (iv) rhinitis with asthma. We then evaluated associations with smoking and BMI in each group. Results The overall age‐adjusted prevalence of rhinitis was 35.1% in men and 39.3% in women. A higher prevalence was observed in the younger population than in the older population. Active smoking and obesity were positively associated with asthma without rhinitis. In contrast, particularly in the 20‐ to 44‐year age‐group, active smoking and obesity were negatively associated with rhinitis without asthma. Conclusion The results of the present study suggest that smoking and obesity may have different effects on the development of rhinitis and asthma.
Population study of the importance of rheumatoid factor isotypes in adults.
Authors: T Jonsson, J Thorsteinsson, A Kolbeinsson, E Jonasdottir, N Sigfusson, H Valdimarsson
Journal: Annals of the Rheumatic Diseases (1992)

Blood samples collected from 13,858 randomly selected subjects participating in a health survey in Iceland from 1974 to 1983 were tested for rheumatoid factor. Samples that were positive in a sensitive RF screening test were analysed further by the Rose-Waaler technique and an isotype specific enzyme linked immunosorbent assay (ELISA). In 1987 the 173 available participants who were RF positive and 156 matched RF negative controls were evaluated clinically for rheumatoid diseases. RF levels and isotype patterns were more persistent in the patients with rheumatoid arthritis (RA) than in RF positive subjects who did not have overt RA. The prevalence of RA was only 19% in the participants who were RF positive in 1987. Forty per cent of the participants who had a persistent (four to 13 years) increase of IgA RF combined with either IgM or IgG RF were diagnosed as having RA. A positive correlation was found between RF levels and various manifestations of RA. This association was stronger for the IgA and IgG RF isotypes than for IgM RF. Excluding RF positivity as a diagnostic parameter, RA was diagnosed in 33 of the participants and 20 (61%) of these patients had increased levels of IgM and IgA RF. Patients with RA with bone erosions in their hands had higher levels of IgA RF than patients without erosions, but an association was not found between bone erosions and other RF isotypes. None of the RF negative participants who were symptom free when the original blood sample was taken developed RA during the four to 13 year follow up period. In contrast, five symptom free RF positive participants developed RA during this period. These five patients had all had increased levels of at least two RF isotypes before the onset of their symptoms. It is concluded that the IgA and IgG RF isotypes have a closer association with the clinical parameters of RA than IgM RF. Furthermore, increases in RF can precede clinical manifestations of RA and this applies in particular to the IgA and IgG RF isotypes.
Immunohistochemical localization and bacteriostatic properties of an iron-binding protein from bronchial mucus.
Authors: P L Masson, J F Heremans, J J Prignot, G Wauters
Journal: Thorax (1966)

BACTERIOLOGICAL TECHNIQUE Filter paper discs of the type used in routine bacteriological work were soaked in a 0-5% (w/v) solution of lactoferrin isolated from human milk by means of the method described by Blanc and Isliker (1961b).The solvent 538
Deciphering the Epigenetic Code of Cardiac Myocyte Transcription
Authors: Sebastian Preissl, Martin Schwaderer, Alexandra Raulf, Michael Hesse, Björn A. Grüning, Claudia Köbele, Rolf Backofen, Bernd K. Fleischmann, Lutz Hein, Ralf Gilsbach
Journal: Circulation Research (2015)

Rationale: Epigenetic mechanisms are crucial for cell identity and transcriptional control. The heart consists of different cell types, including cardiac myocytes, endothelial cells, fibroblasts, and others. Therefore, cell type–specific analysis is needed to gain mechanistic insight into the regulation of gene expression in cardiac myocytes. Although cytosolic mRNA represents steady-state levels, nuclear mRNA more closely reflects transcriptional activity. To unravel epigenetic mechanisms of transcriptional control, cell type–specific analysis of nuclear mRNA and epigenetic modifications is crucial. Objective: The aim was to purify cardiac myocyte nuclei from hearts of different species by magnetic- or fluorescent-assisted sorting and to determine the nuclear and cellular RNA expression profiles and epigenetic marks in a cardiac myocyte–specific manner. Methods and Results: Frozen cardiac tissue samples were used to isolate cardiac myocyte nuclei. High sorting purity was confirmed for cardiac myocyte nuclei isolated from mice, rats, and humans. Deep sequencing of nuclear RNA revealed a major fraction of nascent, unspliced RNA in contrast to results obtained from purified cardiac myocytes. Cardiac myocyte nuclear and cellular RNA expression profiles showed differences, especially for metabolic genes. Genome-wide maps of the transcriptional elongation mark H3K36me3 were generated by chromatin-immunoprecipitation. Transcriptome and epigenetic data confirmed the high degree of cardiac myocyte–specificity of our protocol. An integrative analysis of nuclear mRNA and histone mark occurrence indicated a major impact of the chromatin state on transcriptional activity in cardiac myocytes. Conclusions: This study establishes cardiac myocyte–specific sorting of nuclei as a universal method to investigate epigenetic and transcriptional processes in cardiac myocytes of different origins. These data sets provide novel insight into cardiac myocyte transcription.
Association of Specific Genotypes in Metastatic Suppressor HTPAP with Tumor Metastasis and Clinical Prognosis in Hepatocellular Carcinoma
Authors: Ning Ren, Jin-Cai Wu, Qiong-Zhu Dong, Hai-Jing Sun, Hu-Liang Jia, Guo-Cai Li, Bing-Sheng Sun, Chun Dai, Jiong Shi, Jin-Wang Wei, Yuan-Yuan Sheng, Hai-Jun Zhou, Qing-Hai Ye, Lun-Xiu Qin
Journal: Cancer Research (2011)

Abstract The phosphatidic acid phosphatase HTPAP has been defined as a metastatic suppressor of hepatocellular carcinoma (HCC), but little is known about its function or potential applications as a prognostic marker. In this study, we analyzed patterns of HTPAP genetic variation and gene expression in 864 patients who underwent HCC resection, assessing these patterns for correlations to tumor metastasis potential. Focusing on two tagSNPs that were selected (+357G/C and +1838A/G), we found that only the +357G/C genotype was significantly associated with HTPAP mRNA and protein expression levels and the probability of metastasis. In an independent cohort of 665 HCC patients, we determined that the +357G/C genotype was associated with shorter time to recurrence and overall survival. Together, these results indicated that the HTPAP tagSNP +357 GG+GC genotypes may influence HCC metastatic potential and clinical prognosis by down-regulating HTPAP expression. Extending these results, a global expression profiling analysis identified 41 genes including the pro-inflammatory genes IL-8 and TLR2 that were significantly overexpressed in the +357 GG+GC group, as possible coregulated markers with HTPAP. Together, our findings identify an HTPAP genotype and associated gene expression pattern that favors metastasis progression and that could be used to predict tumor metastasis and prognosis in HCC patients. Cancer Res; 71(9); 3278–86. ©2011 AACR.
Interactions between angiotensin peptides and the sympathetic nervous system mediating intestinal sodium and water absorption in the rat.
Authors: N R Levens, M J Peach, R M Carey
Journal: Journal of Clinical Investigation (1981)

The purpose of this study was to determine the locus of interaction of angiotensin peptides with the sympathetic nervous system leading to alterations in jejunal sodium and water transport. At low physiological doses, angiotensin II (AII) stimulates jejunal sodium and water absorption, while at high doses peptide inhibits absorption and/or stimulates secretion. Both the stimulation of jejunal transport and the inhibition of absorption were expressed in adrenalectomized rats. However, the stimulation of jejunal water absorption was abolished and a potentiated inhibition of transport was expressed in peripherally sympathectomized rats (intact adrenal medulla) and in normal rats after administration of guanethadine, phentolamine, and prazosin. The angiotensin analog (Sar1 Leu8)-AII has low efficacy and is a potent competitive antagonist of the parent peptide in pressor and myotropic systems, but is a full agonist with even greater potency than AII in stimulating jejunal transport. The increased water transport in response to (Sar1 Leu8)-AII is not secondary to enhanced renal renin release, as the analog also stimulated jejunal transport in the presence of captopril and after bilateral nephrectomy. The stimulation of absorption in response to (Sar1 Leu8)-AII alone or together with AII was abolished by phentolamine. These data demonstrate that AII-increased intestinal absorption is secondary to the release of norepinephrine from nerve endings in the jejunum and that AII inhibition of absorption is not mediated by the sympathetic nervous system. The analog (Sar1 Leu8)-AII is a full agonist in the stimulation of jejunal transport (increased norepinephrine release), but antagonizes the inhibitory response to high doses of AII. Angiotensin peptides are potent modulators of intestinal sodium and water absorption.