tbuckley/cabot-search huggingface dataset:
Effects of Intravenous Administration of Slow-Reacting Substance of Anaphylaxis, Histamine, Bradykinin, and Prostaglandin F2α on Pulmonary Mechanics in the Guinea Pig
Authors: Jeffrey M. Drazen, K. Frank Austen
Journal: Journal of Clinical Investigation (1974)

The effects of intravenous administration of a purified preparation of slow-reacting substance of anaphylaxis (SRS-A), histamine, bradykinin, and prostaglandin F2α (PGF2α) on the mechanics of respiration were assessed in the unanesthetized guinea pig. Geometrically increasing doses of SRS-A resulted in graded decreases in average pulmonary compliance, with only modest increases in average pulmonary resistance. A dose with apparent maximal effects. 3,000 U/kg, resulted in a decrease of 49±7% of compliance below control values, with an increase in resistance of 24±8% above control. Intravenous administration of geometrically increasing amounts of histamine, bradykinin, and prostaglandin F2α also resulted in decreased compliance; but in each case this was accompanied by a marked increase in respiratory resistance. A decrease of compliance of approximately 50%, induced by intravenous histamine, bradykinin, or PGF2α, was accompanied by an increase of 60-140% in resistance. Thus, intravenously administered SRS-A alters pulmonary mechanics with a more peripheral effect than any of the other agents tested.
Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis
Authors: Vikram P Sharma, Aimée L Fenwick, Mia S Brockop, Simon J McGowan, Jacqueline A C Goos, A Jeannette M Hoogeboom, Angela F Brady, Nu Owase Jeelani, Sally Ann Lynch, John B Mulliken, Dylan J Murray, Julie M Phipps, Elizabeth Sweeney, Susan E Tomkins, Louise C Wilson, Sophia Bennett, Richard J Cornall, John Broxholme, Alexander Kanapin, David Johnson, Steven A Wall, Peter J van der Spek, Irene M J Mathijssen, Robert E Maxson, Stephen R F Twigg, Andrew O M Wilkie
Journal: Nature Genetics (2013)
Carcinoembryonic Antigen Messenger RNA Expression Using Nested Reverse Transcription-PCR in the Peripheral Blood During Follow-up Period of Patients Who Underwent Curative Surgery for Biliary-Pancreatic Cancer
Authors: Yuko Mataki, Sonshin Takao, Kousei Maemura, Shinichiro Mori, Hiroyuki Shinchi, Shoji Natsugoe, Takashi Aikou
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Outcome for patients with biliary-pancreatic cancer is still poor, despite curative operation. We investigated the clinical significance of molecular detection of circulating cancer cells in the blood as an early indicator of relapse during follow-up of patients who underwent a curative operation for biliary-pancreatic cancer. Patients and Methods: We followed 53 patients who underwent a curative operation for biliary-pancreatic cancer between 1996 and 2001. We used reverse transcription-PCR in the peripheral blood to evaluate carcinoembryonic antigen (CEA) mRNA expression for molecular detection of circulating cancer cells. Follow-up examinations every 3 months after surgery included CEA mRNA expression in the blood, serum CEA, serum carbohydrate antigen 19-9 (CA19-9), and computed tomography or magnetic resonance imaging. Results: Sixteen of 53 patients (30.2%) were diagnosed with a recurrence by imaging studies. The CEA mRNA detection rate in the peripheral blood of these 16 patients was 75% compared with 5.4% in the 37 patients without relapse (P &amp;lt; 0.001). Sensitivity of CEA mRNA, CEA, and CA19-9 serum levels was 75.0%, 50.0%, and 68.8%, respectively. Similarly, specificity was 94.6%, 64.9%, and 81.1%, respectively. CEA mRNA was expressed in the blood, even though tumor markers CEA and CA19-9 were within the normal range in patients with relapse. CEA mRNA expression in the blood, as well as the serum level of CA19-9, tended to be detected a few months earlier than detection by imaging modalities. Conclusions: During the follow-up of patients who undergo a curative operation for biliary-pancreatic cancer, CEA mRNA expression in the peripheral blood might be a useful and early indicator of relapse.
Testosterone perturbs systemic iron balance through activation of epidermal growth factor receptor signaling in the liver and repression of hepcidin
Authors: Chloé Latour, Léon Kautz, Céline Besson-Fournier, Marie-Laure Island, François Canonne-Hergaux, Olivier Loréal, Tomas Ganz, Hélène Coppin, Marie-Paule Roth
Journal: Hepatology (2013)

Gender-related disparities in the regulation of iron metabolism may contribute to the differences exhibited by men and women in the progression of chronic liver diseases associated with reduced hepcidin expression, e.g., chronic hepatitis C, alcoholic liver disease, or hereditary hemochromatosis. However, their mechanisms remain poorly understood. In this study we took advantage of the major differences in hepcidin expression and tissue iron loading observed between Bmp6-deficient male and female mice to investigate the mechanisms underlying this sexual dimorphism. We found that testosterone robustly represses hepcidin transcription by enhancing Egfr signaling in the liver and that selective epidermal growth factor receptor (Egfr) inhibition by gefitinib (Iressa) in males markedly increases hepcidin expression. In males, where the suppressive effects of testosterone and Bmp6-deficiency on hepcidin expression are combined, hepcidin is more strongly repressed than in females and iron accumulates massively not only in the liver but also in the pancreas, heart, and kidneys. Testosterone-induced repression of hepcidin expression becomes functionally important during homeostatic stress from disorders that result in iron loading and/or reduced capacity for hepcidin synthesis. These findings suggest that novel therapeutic strategies targeting the testosterone/EGF/EGFR axis may be useful for inducing hepcidin expression in patients with iron overload and/or chronic liver diseases.
Influence of peppermint oil on absorptive and secretory processes in rat small intestine.
Authors: A Beesley, J Hardcastle, P T Hardcastle, C J Taylor
Journal: Gut (1996)

BACKGROUND: Peppermint oil is used to relieve the symptoms of irritable bowel syndrome, relaxing intestinal smooth muscle by reducing the availability of calcium, but its effects on intestinal transport are unknown. AIMS: To determine the effect of peppermint oil on intestinal transport processes. METHODS: The influence of peppermint oil on intestinal transport was investigated in rat jejunum using both intestinal sheets mounted in Ussing chambers and brush border membrane vesicles. RESULTS: Mucosal peppermint oil (1 and 5 mg/ml) had no significant effect on basal short circuit current, but inhibited the increase associated with sodium dependent glucose absorption. The increased short circuit current induced by serosal acetylcholine, a reflection of calcium mediated electrogenic chloride secretion, was unaffected by mucosal peppermint oil (5 mg/ml). In contrast, serosal peppermint oil (1 mg/ml) inhibited the response to acetylcholine without reducing the effect of mucosal glucose. In brush border membrane vesicles active glucose uptake was inhibited by extravesicular peppermint oil at concentrations of 0.5 and 1 mg/ml. CONCLUSIONS: Peppermint oil in the intestinal lumen inhibits enterocyte glucose uptake via a direct action at the brush border membrane. Inhibition of secretion by serosal peppermint oil is consistent with a reduced availability of calcium.
Phase I Study of Temsirolimus in Pediatric Patients With Recurrent/Refractory Solid Tumors
Authors: Sheri L. Spunt, Stephan A. Grupp, Terry A. Vik, Victor M. Santana, David J. Greenblatt, Jill Clancy, Anna Berkenblit, Mizue Krygowski, Revathi Ananthakrishnan, Joseph P. Boni, Richard J. Gilbertson
Journal: Journal of Clinical Oncology (2011)

Purpose To determine dose-limiting toxicities, maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of weekly intravenous temsirolimus, a mammalian target of rapamycin (mTOR) signaling pathway inhibitor, in pediatric patients with recurrent or refractory solid tumors. Patients and Methods Cohorts of three to six patients 1 to 21 years of age with recurrent or refractory solid tumors were treated with a 1-hour intravenous infusion of temsirolimus weekly for 3 weeks per course at one of four dose levels: 10, 25, 75, or 150 mg/m 2 . During the first two courses, pharmacokinetic and pharmacodynamic evaluations (phosphorylation of S6, AKT, and 4EBP1 in peripheral-blood mononuclear cells) were performed. Results Dose-limiting toxicity (grade 3 anorexia) occurred in one of 18 evaluable patients at the 150 mg/m 2 level, which was determined to be tolerable, and an MTD was not identified. In 13 patients evaluable for response after two courses of therapy, one had complete response (CR; neuroblastoma) and five had stable disease (SD). Four patients (three SDs + one CR) remained on treatment for more than 4 months. The sum of temsirolimus and sirolimus areas under the concentration-time curve was comparable to values in adults. AKT and 4EBP1 phosphorylation were inhibited at all dose levels, particularly after two courses. Conclusion Weekly intravenous temsirolimus is well tolerated in children with recurrent solid tumors, demonstrates antitumor activity, has pharmacokinetics similar to those in adults, and inhibits the mTOR signaling pathway in peripheral-blood mononuclear cells. Further studies are needed to define the optimal dose for use in combination with other antineoplastic agents in pediatric patients.
Detection of Epstein-Barr virus DNA by polymerase chain reaction in blood and tissue biopsies from patients with Sjogren's syndrome.
Authors: I Saito, B Servenius, T Compton, R I Fox
Journal: The Journal of Experimental Medicine (1989)

Polymerase chain reaction has been used to detect increased levels of EBV DNA in salivary gland (SG) biopsies and PBL from patients with Sjogren's syndrome (SS). These results suggest that EBV, which has a normal site of latency in a small number of SG epithelial cells, may be reactivated in SS patients and provide a target for immune attack. The great sensitivity of polymerase chain reaction (PCR) and the ability to analyze very small tissue biopsies (37) make this technique well suited for clinical diagnosis. Specific methods to prevent artefactual contamination of tissue biopsy DNA with viral DNA of other samples (i.e., lyophilization of samples before DNA extraction) and the use of an internal positive control (i.e., inclusion of primers for a single copy human gene) during PCR amplification are presented. Since EBV reactivation occurs with markedly increased frequency in patients with lymphoproliferative and immunodeficiency diseases, as well as transplant recipients receiving cyclosporin A (10), rapid methods of viral detection such as PCR may allow better monitoring of medications and early detection of EBV-related lymphomas that may arise in these patients.
Interconversions of Apolipoprotein Fragments
Authors: C B Blum, R I Levy
Journal: Annual Review of Medicine (1975)

Over the past decade attention has focused on the protein moieties of the lipo­ proteins, the lipoprotein apoproteins. It has become clear that they hold the key to our understanding of normal as well as abnormal lipid transport. We have realized that there is a heterogeneous group of lipoprotein apoproteins that differ biologi­ cally, immunologically, and physicochemically, some with apparently only struc­ tural, others with more functional roles in normal lipoprotein metabolism.
Relationship between the Arg72Pro Polymorphism of p53 and outcome for patients with traumatic brain injury
Authors: Pascual Martínez-Lucas, Jerónimo Moreno-Cuesta, Dolores C. García-Olmo, Francisco Sánchez-Sánchez, Julio Escribano-Martínez, Ana Cuartero del Pozo, Máxima Lizán-García, Damián García-Olmo
Journal: Intensive Care Medicine (2005)
Comparative adrenal suppression with inhaled budesonide and fluticasone propionate in adult asthmatic patients.
Authors: D J Clark, A Grove, R I Cargill, B J Lipworth
Journal: Thorax (1996)

BACKGROUND: A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis, each given by metered dose inhaler to asthmatic patients. METHODS: Twelve asthmatic patients of mean age 29.9 years, with a forced expiratory volume in one second (FEV1) 92.9% predicted and forced expiratory flow 25-75% (FEF25-75) 69.5% predicted, on less than or equal to 400 micrograms/day inhaled corticosteroid, were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400, 1000, 1600, 2000 micrograms and fluticasone propionate 500, 1000, 1500, 2000 micrograms. Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later. RESULTS: Serum cortisol levels compared with placebo (mean 325.2 nmol/l) were suppressed by fluticasone at doses of 1500 micrograms (211.6 nmol/l) and 2000 micrograms (112.3 nmol/l) and by budesonide at 2000 micrograms (243.4 nmol/l). Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms (95% CI for difference 42.9 to 219.2). The dose ratio (geometric mean) for the relative potency was 2.89 fold (95% CI 1.19 to 7.07). In terms of percentage suppression versus placebo, fluticasone propionate also produced greater effects (means and 95% CI for difference): budesonide 1600 micrograms (16.0) versus fluticasone propionate 1500 micrograms (40.9) (95% CI -0.6 to 50.6), budesonide 2000 micrograms (26.0) versus fluticasone 2000 micrograms (65.2) (95% CI 10.5 to 67.8). Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range (150 nmol/l) for fluticasone and five of 24 for budesonide. Fluticasone propionate also caused greater ACTH suppression than budesonide (as % versus placebo): budesonide 1600 micrograms (12.0) versus fluticasone propionate 1500 micrograms (31.9) (95% CI 7.6 to 32.1), budesonide 2000 micrograms (13.5) versus fluticasone propionate 2000 micrograms (44.4) (95% CI 13.2 to 48.7). For overnight 10 hour urinary cortisol (nmol/10 hours) there was a difference between the lowest doses of the two drugs: budesonide 400 micrograms (37.2) versus fluticasone propionate 500 micrograms (19.9) (95% CI 6.9 to 27.8). CONCLUSIONS: Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption. Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients.
Accuracy of the 5-Day FreeStyle Navigator Continuous Glucose Monitoring System
Authors: Richard L. Weinstein, Sherwyn L. Schwartz, Ronald L. Brazg, Jolyon R. Bugler, Thomas A. Peyser, Geoffrey V. McGarraugh
Journal: Diabetes Care (2007)

OBJECTIVE—The purpose of this study was to compare the accuracy of measurements of glucose in interstitial fluid made with the FreeStyle Navigator Continuous Glucose Monitoring System with Yellow Springs Instrument laboratory reference measurements of venous blood glucose. RESEARCH DESIGN AND METHODS—Fifty-eight subjects with type 1 diabetes, aged 18–64 years, were enrolled in a multicenter, prospective, single-arm study. Each subject wore two sensors simultaneously, which were calibrated with capillary fingerstick measurements at 10, 12, 24, and 72 h after insertion. Measurements from the FreeStyle Navigator system were collected at 1-min intervals and compared with venous measurements taken once every 15 min for 50 h over the 5-day period of sensor wear in an in-patient clinical research center. Periods of high rates of change of glucose were induced by insulin and glucose challenges. RESULTS—Comparison of the FreeStyle Navigator measurements with the laboratory reference method (n = 20,362) gave mean and median absolute relative differences (ARDs) of 12.8 and 9.3%, respectively. The percentage in the clinically accurate Clarke error grid A zone was 81.7% and that in the in the benign error B zone was 16.7%. During low rates of change (&amp;lt;±1 mg · dl−1 · min−1), the percentage in the A zone was higher (84.9%) and the mean and median ARDs were lower (11.7 and 8.5%, respectively). CONCLUSIONS—Measurements with the FreeStyle Navigator system were found to be consistent and accurate compared with venous measurements made using a laboratory reference method over 5 days of sensor wear (82.5% in the A zone on day 1 and 80.9% on day 5).
Expression Divergence between Escherichia coli and Salmonella enterica serovar Typhimurium Reflects Their Lifestyles
Authors: Pieter Meysman, Aminael Sánchez-Rodríguez, Qiang Fu, Kathleen Marchal, Kristof Engelen
Journal: Molecular Biology and Evolution (2013)

Escherichia coli K12 is a commensal bacteria and one of the best-studied model organisms. Salmonella enterica serovar Typhimurium, on the other hand, is a facultative intracellular pathogen. These two prokaryotic species can be considered related phylogenetically, and they share a large amount of their genetic material, which is commonly termed the "core genome." Despite their shared core genome, both species display very different lifestyles, and it is unclear to what extent the core genome, apart from the species-specific genes, plays a role in this lifestyle divergence. In this study, we focus on the differences in expression domains for the orthologous genes in E. coli and S. Typhimurium. The iterative comparison of coexpression methodology was used on large expression compendia of both species to uncover the conservation and divergence of gene expression. We found that gene expression conservation occurs mostly independently from amino acid similarity. According to our estimates, at least more than one quarter of the orthologous genes has a different expression domain in E. coli than in S. Typhimurium. Genes involved with key cellular processes are most likely to have conserved their expression domains, whereas genes showing diverged expression are associated with metabolic processes that, although present in both species, are regulated differently. The expression domains of the shared "core" genome of E. coli and S. Typhimurium, consisting of highly conserved orthologs, have been tuned to help accommodate the differences in lifestyle and the pathogenic potential of Salmonella.
Use of total lymphocyte count for informing when to start antiretroviral therapy in HIV-infected children: a meta-analysis of longitudinal data
Authors: DT Dunn, DM Gibb, T Duong, AG Babiker, IP Aboulker, M Bulterys, M Cortina-Borja, C Gabiano, L Galli, C Giaquinto, Harris, M Hughes, R McKinney, J Moye, ML Newell, S Pahwa, P Palumbo, C Rudin, M Sharland, W Shearer, B Thompson, P Tookey, Hiv Paediat Prognostic Markers Col
Journal: The Lancet (2005)
Partial Versus Full Hospitalization for Adults in Psychiatric Distress: A Systematic Review of the Published Literature (1957–1997)
Authors: Marcela Horvitz-Lennon, Sharon-Lise T. Normand, Peter Gaccione, Richard G. Frank
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors reviewed published research that compared partial and full hospitalization as alternative programs for the care of mentally ill adults, with the goal of both systematizing the knowledge base and providing directions for future research. METHOD: Studies published since 1950 were obtained through manual and electronic searches. Results were stratified by outcome domain, type of measure used to report between-group differences (global, partial, or rate-based), and time of assessment. Effect sizes were computed and combined within a random-effects framework. RESULTS: Eighteen investigations published between 1957 and 1997 were systematically reviewed. Over half of eligible patients were excluded a priori; diagnostic severity of enrollees varied widely. On measures of psychopathology, social functioning, family burden, and service utilization, the authors found no evidence of differential outcome in the selected patient population admitted to the studies reviewed. Rates of satisfaction with services suggested an advantage for partial hospitalization within 1 year of discharge, with the gap being largest at 7–12 months. CONCLUSIONS: Although partial hospitalization is not an option for all patients requiring intensive services, outcomes of partial hospitalization patients in these studies were no different from those of inpatients. Further, patients and families were more satisfied with partial hospitalization in the short term. Weaknesses of the studies limited the scope of our inquiry and the generalizability of findings. Positive findings require replication under the present circumstances of mental health care, and more research is needed to identify predictors of differential outcome and successful partial hospitalization. A clearer definition of partial hospitalization will help consolidate its role in the continuum of mental health services.
The Association of Comorbid Depression With Mortality in Patients With Type 2 Diabetes
Authors: Wayne J. Katon, Carolyn Rutter, Greg Simon, Elizabeth H.B. Lin, Evette Ludman, Paul Ciechanowski, Leslie Kinder, Bessie Young, Michael Von Korff
Journal: Diabetes Care (2005)

OBJECTIVE—We assessed whether patients with comorbid minor and major depression and type 2 diabetes had a higher mortality rate over a 3-year period compared with patients with diabetes alone. RESEARCH DESIGN AND METHODS—In a large health maintenance organization (HMO), 4,154 patients with type 2 diabetes were surveyed and followed for up to 3 years. Patients initially filled out a written questionnaire, and HMO-automated diagnostic, laboratory, and pharmacy data and Washington State mortality data were collected to assess diabetes complications and deaths. Cox proportional hazards regression models were used to calculate adjusted hazard ratios of death for each group compared with the reference group. RESULTS—There were 275 (8.3%) deaths in 3,303 patients without depression compared with 48 (13.6%) deaths in 354 patients with minor depression and 59 (11.9%) deaths among 497 patients with major depression. A proportional hazards model with adjustment for age, sex, race/ethnicity, and educational attainment found that compared with the nondepressed group, minor depression was associated with a 1.67-fold increase in mortality (P = 0.003), and major depression was associated with a 2.30-fold increase (P &amp;lt; 0.0001). In a second model that controlled for multiple potential mediators, both minor and major depression remained significant predictors of mortality. CONCLUSIONS—Among patients with diabetes, both minor and major depression are strongly associated with increased mortality. Further research will be necessary to disentangle causal relationships among depression, behavioral risk factors (adherence to medical regimens), diabetes complications, and mortality.
Laparoscopic ultrasonography versus intra-operative cholangiogram for the detection of common bile duct stones during laparoscopic cholecystectomy: A meta-analysis of diagnostic accuracy
Authors: Omer Aziz, Hutan Ashrafian, Catherine Jones, Leanne Harling, Sacheen Kumar, George Garas, Thomas Holme, Ara Darzi, Emmanouil Zacharakis, Thanos Athanasiou
Journal: International Journal of Surgery (2014)