tbuckley/cabot-search huggingface dataset:
Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.
Authors: G A FitzGerald, J A Oates, J Hawiger, R L Maas, L J Roberts, J A Lawson, A R Brash
Journal: Journal of Clinical Investigation (1983)

To assess the pharmacologic effects of aspirin on endogenous prostacyclin and thromboxane biosynthesis, 2,3-dinor-6-keto PGF1 alpha (PGI-M) and 2,3-dinor-thromboxane B2 (Tx-M) were measured in urine by mass spectrometry during continuing administration of aspirin. To define the relationship of aspirin intake to endogenous prostacyclin biosynthesis, sequential urines were initially collected in individuals prior to, during, and subsequent to administration of aspirin. Despite inter- and intra-individual variations, PGI-M excretion was significantly reduced by aspirin. However, full mass spectral identification confirmed continuing prostacyclin biosynthesis during aspirin therapy. Recovery of prostacyclin biosynthesis was incomplete 5 d after drug administration was discontinued. To relate aspirin intake to indices of thromboxane biosynthesis and platelet function, volunteers received 20 mg aspirin daily followed by 2,600 mg aspirin daily, each dose for 7 d in sequential weeks. Increasing aspirin dosage inhibited Tx-M excretion from 70 to 98% of pretreatment control values; platelet TxB2 formation from 4.9 to 0.5% and further inhibited platelet function. An extended study was performed to relate aspirin intake to both thromboxane and prostacyclin generation over a wide range of doses. Aspirin, in the range of 20 to 325 mg/d, resulted in a dose-dependent decline in both Tx-M and PGI-M excretion. At doses of 325-2,600 mg/d Tx-M excretion ranged from 5 to 3% of control values while PGI-M remained at 37-23% of control. 3 d after the last dose of aspirin (2,600 mg/d) mean Tx-M excretion had returned to 85% of control, whereas mean PGI-M remained at 40% of predosing values. Although the platelet aggregation response (Tmax) to ADP ex vivo was inhibited during administration of the lower doses of aspirin the aggregation response returned to control values during the final two weeks of aspirin administration (1,300 and 2,600 mg aspirin/d) despite continued inhibition of thromboxane biosynthesis. These results suggest that although chronic administration of aspirin results in inhibition of endogenous thromboxane and prostacyclin biosynthesis over a wide dose range, inhibition of thromboxane biosynthesis is more selective at 20 than at 2,600 mg aspirin/d. However, despite this, inhibition of platelet function is not maximal at the lower aspirin dosage. Doses of aspirin in excess of 80 mg/d resulted in substantial inhibition of endogenous prostacyclin biosynthesis. Thus, it is unlikely that any dose of aspirin can maximally inhibit thromboxane generation without also reducing endogenous prostacyclin biosynthesis. These results also indicate that recovery of endogenous prostacyclin biosynthesis is delayed following aspirin administration and that the usual effects of aspirin on platelet function ex vivo may be obscured during chronic aspirin administration in man.
1187 PK–PD MODELING IN A SUB-GROUP OF PATIENTS TREATED WITH GS-7977 AND RIBAVIRIN SHOWED A SIGNIFICANTLY SLOWER EARLY VIRAL KINETICS IN RELAPSERS
Authors: D. Bon, E. Herrmann, B. Shivakumar, Y.-J. Lee, L. Heytens, M. Polis, H. Masur, A.U. Neumann, W.T. Symonds, J. McHutchison, S. Kottilil, A. Osinusi
Journal: Journal of Hepatology (2013)
The Renal-Specific Transporter Mediates Facilitative Transport of Organic Anions at the Brush Border Membrane of Mouse Renal Tubules
Authors: Tomoki Imaoka, Hiroyuki Kusuhara, Satomi Adachi-Akahane, Maki Hasegawa, Naomi Morita, Hitoshi Endou, Yuichi Sugiyama
Journal: Journal of the American Society of Nephrology (2004)

The renal secretion of organic anions across the proximal tubules is achieved by a coordination of uptake and efflux transporters. This study reports the expression, localization, and functional properties of mouse renal-specific transporter (RST). Mouse RST mRNA is predominantly expressed in the kidney and localized on the brush border membrane of mouse kidney proximal tubules. Mouse RST-expressing HEK293 cells exhibited saturable uptake of p-aminohippurate (Km approximately 234 microM), which was increased by an increase in K(+) concentration or in the presence of Ba(2+) and ouabain and decreased by diethylpyrocarbonate, a histidine modifier. An increase in K(+) concentration enhanced the uptake of benzylpenicillin, 2,4-dichlorophenoxyacetate, and dehydroepiandrosterone sulfate, suggesting polyspecific substrate specificity of mouse RST. Vectorial transport of 2,4-dichlorophenoxyacetate was observed in the basal-to-apical direction in rat organic anion transporter 3-expressing LLC-PK1 cells (rOat3-LLC); however, coexpression of mouse RST in rOat3-LLC caused a 1.3-fold increase in the basal-to-apical transport. In addition, the basal-to-apical transport of benzylpenicillin and urate was 3- and 2.5-fold greater than that in the opposite direction in the double-transfected cells, respectively, whereas their transepithelial transport in vector- or rOat3-LLC was symmetrical. Furthermore, the basal-to-apical transport of benzylpenicillin was saturable and reduced by increasing extracellular K(+) concentration and ouabain. These results suggest that mouse RST mediates the efflux of organic anions including urate and works as exit for organic anions in the proximal tubules. In addition to the kidney, mouse RST was detected in the brain capillaries and the choroid plexus, and it may also play a role in efflux transport of organic anions across the barriers of the central nervous system.
Fallibility of transthoracic needle biopsy of anterior mediastinal masses.
Authors: L A Robinson, J R Dobson, P J Bierman
Journal: Thorax (1995)

Percutaneous transthoracic core needle biopsy has been advocated as a highly accurate technique for the diagnosis of anterior mediastinal masses. A patient is described with a large anterior mediastinal mass in whom the diagnosis of mediastinal carcinoid tumour was made by transthoracic core needle biopsy. At definitive surgical resection the tumour proved to be a B cell lymphoma. This case illustrates one of the important limitations of needle biopsy with its potential for sampling error.
Effects of anti-mite measures on children with mite-sensitive asthma: a controlled trial.
Authors: M L Burr, B V Dean, T G Merrett, E Neale, A S St Leger, E R Verrier-Jones
Journal: Thorax (1980)

Mite counts and tests for mite antigen were performed on samples of dust taken from the bedding of 53 children with mite-sensitive asthma. The samples from damp houses and the beds or enuretic children had markedly more mites and mite-antigen than those from dry houses. although the predominant species was usually Dermatophagoides pteronyssinus, some of the beds in the damp houses were heavily infested with another pyroglyphid mite Euroglyphus maynei, so that this was the species found in the greatest numbers. D pteronyssinus antigen was found to be correlated broadly with the total mite count, but more antigen was present for a given number of mites in the mattresses than in the blankets. The children were randomly allocated into two groups, one of which carried out rigorous anti-mite measures. The amounts of dust and mite antigen were reduced, though not the numbers of mites. Peak flow readings were monitored in the two groups for eight weeks and a final assessment made by a paediatrician who was unaware of the allocation of each patient in the trial. No significant differences emerged in the progress of the two groups, both tending to improve. Measures designed to remove mites from bedding do not greatly benefit the majority of children with mite-sensitive asthma.
Management of Uncontrolled Hypertension in a Nurse-Led Clinic Compared With Conventional Care for Patients with Type 2 Diabetes
Authors: Elizabeth A. Denver, Maria Barnard, Robin G. Woolfson, Kenneth A. Earle
Journal: Diabetes Care (2003)

OBJECTIVE—To compare the effectiveness of a nurse-led hypertension clinic with conventional community care in general practice in the management of uncontrolled hypertension in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—We studied 120 men and women outpatient attendees (61% non-Caucasian) with type 2 diabetes and a seated blood pressure (BP) ≥140/80 mmHg. All patients were being treated for hypertension, and 71% had increased urinary albumin excretion (UAE). Patients were allocated to either a nurse-led hypertension clinic or conventional primary care. The primary outcome measure was a change in systolic BP. Secondary outcome measures were total cholesterol, HDL cholesterol, total triglycerides, HbA1c, UAE, serum creatinine, and changes in absolute stroke and coronary heart disease (CHD) risk scores. RESULTS—The mean (95% CI) difference in the decrement of systolic BP was 12.6 mmHg (5.9–19.3) (P = 0.000) in favor of the nurse-led group, whose patients were three times more likely to a reach target systolic BP &amp;lt;140 mmHg compared with conventional care (P = 0.003). A significant fall in 10-year CHD (P = 0.004) and stroke risk (P = 0.000) scores occurred only in the nurse-led group. There were no significant differences in the reduction of diastolic BP or any of the other secondary outcome measures at 6 months. CONCLUSIONS—Compared with conventional care, a nurse-led hypertension clinic is a more effective intervention for patients with type 2 diabetes and uncontrolled hypertension. A target systolic BP &amp;lt;140 mmHg is more readily achieved and may be associated with significant reductions in 10-year cardiovascular disease risk scores.
Steroidogenic Factor 1: A Key Determinant of Endocrine Development and Function
Authors: Keith L. Parker, Bernard P. Schimmer
Journal: Endocrine Reviews (1997)

I. Introduction II. The Initial Identification of SF-1 as a Key Determinant of Steroid Hormone Biosynthesis A. Overview of steroidogenesis B. SF-1 and the regulation of steroidogenesis C. Cloning and structural characterization of SF-1 1. Structural features of SF-1 2. Multiple transcripts are encoded by the gene encoding SF-1 3. The gene encoding SF-1 is evolutionarily conserved in vertebrates and invertebrates III. Characterization of Sites of SF-1 Expression and Identification of Its Target Genes A. Profiles of SF-1 expression 1. Adult steroidogenic tissues 2. Embryonic steroidogenic tissues 3. Other sites of SF-1 expression B. Target genes regulated by SF-1 1. Steroidogenic cells 2. Sertoli cells 3. Gonadotropes 4. VMH IV. The Roles Of SF-1 in Vivo: Targeted Gene Disruption to Create SF-1 Knockout Mice A. General features of the SF-1 knockout mice B. Primary steroidogenic tissues in SF-1 knockout mice C. Pituitary and hypothalamic defects in SF-1 knockout mice V. Perspectives and Future Directions A. ...
Clinical Significance of Osteoprotegerin Expression in Human Colorectal Cancer
Authors: Shunsuke Tsukamoto, Toshiaki Ishikawa, Satoru Iida, Megumi Ishiguro, Kaoru Mogushi, Hiroshi Mizushima, Hiroyuki Uetake, Hiroshi Tanaka, Kenichi Sugihara
Journal: Clinical Cancer Research (2011)

This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC).The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells, especially in patients with distant metastases, was a prerequisite to select candidate genes. The mRNA expression of candidate genes was investigated by quantitative reverse transcriptase PCR (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study and investigated the relationship between protein expression and clinicopathologic features in 274 CRC patients.Using microarray analysis, we identified 6 candidate genes related to distant metastases in CRC patients. Among these genes, osteoprotegerin (OPG) is known to be associated with aggressiveness in several cancers through inhibition of apoptosis via neutralization of the function of TNF-related apoptosis-inducing ligand. The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastases than those without metastases. Overexpression of OPG protein was associated with significantly worse overall survival and relapse-free survival. Moreover, overexpression of the OPG protein was an independent risk factor for CRC recurrence.Overexpression of OPG may be a predictive biomarker of CRC recurrence and a target for treatment of this disease.
Top-down modulation, emotion, and hallucination
Authors: André Aleman, René S. Kahn
Journal: Behavioral and Brain Sciences (2002)

We argue that the pivotal role assigned by Northoff to the principle of top-down modulation in catatonia might successfully be applied to other symptoms of schizophrenia, for example, hallucinations. Second, we propose that Northoff's account would benefit from a more comprehensive analysis of the cognitive level of explanation. Finally, contrary to Northoff, we hypothesize that “top-down modulation” might play as important a role as “horizontal modulation” in affective-behavioral alterations.
Pneumococcal epiglottitis in systemic lupus erythematosus on high-dose corticosteroids.
Authors: M Shalit, D J Gross, Y Levo
Journal: Annals of the Rheumatic Diseases (1982)

An inherited neurological disorder characterized by sustained twisting movements during waking has been discovered in Sprague-Dawley rats. The mutation follows an autosomal recessive pattern of inheritance and has been named dystonic (dt). The rat mutants are indistinguishable from normal littermates in open field behavior and climbing activity prior to postnatal days 9 to 10. Clinical signs begin to appear on day 10 and include twisting of the axial musculature, hyperflexion of the trunk, self-clasping of forelimbs and hindlimbs, and poor placement of the limbs during locomotion. No morphological lesions of neural or non- neural tissues have been observed with routine light microscopy. Dystonic rats demonstrate significantly elevated cerebellar norepinephrine levels, although levels in other terminal fields of the locus ceruleus are similar to those of normal littermates. No differences in the pattern or density of noradrenergic innervation were apparent in cerebellar tissue from dt rats examined with histochemical fluorescence techniques. These mutants were less sensitive than unaffected littermates to the akinesic effects of the dopamine blocker haloperidol. However, striatal dopamine levels were not reliably different from normal in dt rats, and their response to the movement- stimulating effects of apomorphine appeared normal. These findings suggest the presence of biochemical disturbances in the extrapyramidal system of dt rats. The dt rat may provide a useful model for human dystonia musculorum deformans.
Cytokines in Sjögren's syndrome: potential therapeutic targets
Authors: Nienke Roescher, Paul P Tak, Gabor G Illei
Journal: Annals of the Rheumatic Diseases (2010)

The dysregulated cytokine network in Sjögren's Syndrome (SS) is reflected by local and systemic overexpression of pro-inflammatory cytokines and absent or low levels of anti-inflammatory cytokines. To date, the use of cytokine based therapies in SS has been disappointing. Oral administration of low dose interferon (IFN) α showed inconsistent efficacy in various studies and failed to achieve the primary endpoint in a pivotal randomised controlled trial. Similarly, neither of the two tumour necrosis factor (TNF)-α blockers tested (etanercept and infliximab) showed efficacy in placebo controlled trials. Although the rationale for low dose oral IFN treatment has not been firmly established, TNF blockade was based on solid preclinical data. Therefore, the reason for the lack of efficacy is unclear, but recent data suggest that unexpected biological effects of TNF antagonists may have contributed to this. Cytokines, given their central role in the pathogenesis of SS, remain attractive targets for future treatments, despite the disappointing early results. Inflammatory cytokines are obvious candidates, and agents against several of them are available or under development for other autoimmune diseases similar to SS. New candidate cytokines such as IL-17 and IL-12 and/or IL-23 may provide promising targets for SS. Additionally, as an alternative to systemic treatment, which has the risk of potentially severe side effects, the use of local cytokine directed therapy should be explored.
Synthetic Chelating Agents in Clinical Medicine
Authors: T N Pullman, A R Lavender, M Forland
Journal: Annual Review of Medicine (1963)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Patient-Physician Communication About Out-of-Pocket Costs
Authors: G Caleb Alexander, Lawrence P Casalino, David O Meltzer
Journal: JAMA (2003)

Context Out-of-pocket costs account for approximately one fifth of health care expenditures and are increasing.Previous research suggests that these costs are associated with medication nonadherence and considerable economic burden among some patients.Little is known about patient-physician communication regarding these costs.Objective To identify patients' and physicians' beliefs and practices regarding discussions of out-of-pocket costs.Design, Setting, and Participants Cross-sectional paired surveys of 133 general internists and 484 of their outpatients, aged 18 years or older, in 3 academic and 18 community general medicine practices in the Chicago metropolitan area, March-November 2002. Main Outcome MeasuresPatient and physician beliefs regarding discussions of out-of-pocket costs, frequency and predictors of discussions, and physician recognition of patient burden from out-of-pocket costs.Results Sixty-three percent of patients reported a desire to talk with their physician about their out-of-pocket costs, and 79% of physicians believed that patients in general want to discuss these costs.By contrast, only 35% of physicians and 15% of patients reported ever having discussed the study patient's out-of-pocket costs.Multivariate analysis indicated that discussions were significantly more likely to occur with patients burdened by their out-of-pocket costs (prevalence ratio [PR], 2.55; 95% confidence intervals [CI], 1.62-3.76)and with those patients seen in a community practice (PR, 5.19; CI, 1.86-8.93).Among patients burdened by out-of-pocket costs, physicians were substantially more likely to recognize this burden when a prior discussion regarding out-of-pocket costs had taken place (80% vs 51%).Conclusions Among respondents, both patients and physicians believed that discussions of out-of-pocket costs were important, yet these discussions occurred infrequently.Physician communication with patients about out-of-pocket costs may be an important yet neglected aspect of current clinical practice.Further research should identify the prevalence of this problem in broader populations, investigate its causes, and evaluate the impact of enhanced communication about out-of-pocket costs on patient satisfaction, utilization of care, and outcomes.
Tamoxifen and Risk of Contralateral Breast Cancer for <i>BRCA1</i> and <i>BRCA2</i> Mutation Carriers
Authors: Kelly-Anne Phillips, Roger L. Milne, Matti A. Rookus, Mary B. Daly, Antonis C. Antoniou, Susan Peock, Debra Frost, Douglas F. Easton, Steve Ellis, Michael L. Friedlander, Saundra S. Buys, Nadine Andrieu, Catherine Noguès, Dominique Stoppa-Lyonnet, Valérie Bonadona, Pascal Pujol, Sue Anne McLachlan, Esther M. John, Maartje J. Hooning, Caroline Seynaeve, Rob A.E.M. Tollenaar, David E. Goldgar, Mary Beth Terry, Trinidad Caldes, Prue C. Weideman, Irene L. Andrulis, Christian F. Singer, Kate Birch, Jacques Simard, Melissa C. Southey, Håkan L. Olsson, Anna Jakubowska, Edith Olah, Anne-Marie Gerdes, Lenka Foretova, John L. Hopper
Journal: Journal of Clinical Oncology (2013)

To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers.Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up.Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC diagnosis. There were 520 CBCs over 20,104 person-years of observation. The adjusted HR estimates were 0.38 (95% CI, 0.27 to 0.55) and 0.33 (95% CI, 0.22 to 0.50) for BRCA1 and BRCA2 mutation carriers, respectively. After left truncating at recruitment to the cohort, adjusted HR estimates were 0.58 (95% CI, 0.29 to 1.13) and 0.48 (95% CI, 0.22 to 1.05) based on 657 BRCA1 and 426 BRCA2 mutation carriers with 100 CBCs over 4,392 person-years of prospective follow-up. HRs did not differ by estrogen receptor status of the first BC (missing for 56% of cases).This study provides evidence that tamoxifen use is associated with a reduction in CBC risk for BRCA1 and BRCA2 mutation carriers. Further follow-up of these cohorts will provide increased statistical power for future prospective analyses.
Genetic Variants in Pigment Epithelium-Derived Factor Influence Response of Polypoidal Choroidal Vasculopathy to Photodynamic Therapy
Authors: Isao Nakata, Kenji Yamashiro, Ryo Yamada, Norimoto Gotoh, Hideo Nakanishi, Hisako Hayashi, Akitaka Tsujikawa, Atsushi Otani, Sotaro Ooto, Hiroshi Tamura, Masaaki Saito, Kuniharu Saito, Tomohiro Iida, Akio Oishi, Yasuo Kurimoto, Fumihiko Matsuda, Nagahisa Yoshimura
Journal: Ophthalmology (2011)
Chek2 DNA Damage Response Pathway and Inherited Breast Cancer Risk
Authors: Nadine Tung, Daniel P. Silver
Journal: Journal of Clinical Oncology (2011)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2011.37.1476 Journal of Clinical Oncology - published online before print August 29, 2011 PMID: 21876079 Chek2 DNA Damage Response Pathway and Inherited Breast Cancer Risk Nadine TungxNadine TungSearch for articles by this author Daniel P. SilverxDaniel P. SilverSearch for articles by this author Show More Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MADana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2011.37.1476 First Page Full Text PDF Figures and Tables © 2011 by American Society of Clinical Oncology