tbuckley/cabot-search huggingface dataset:
Role of insulin in lipoprotein secretion by cultured rat hepatocytes.
Authors: W Patsch, S Franz, G Schonfeld
Journal: Journal of Clinical Investigation (1983)

To study the effect of insulin on lipoprotein synthesis and secretion by the liver, apoprotein and lipid levels were measured in primary rat liver cell cultures grown on fibronectin-coated dishes. Triglycerides, phospholipids, apoprotein (apo) B, apo-E, and apo-C-III3 all accumulated in culture media linearly for periods up to 20 h. During incubations, cellular triglyceride contents increased slightly, while cellular apoprotein and phospholipid contents remained constant. In the absence of insulin, rates of accumulation in media of triglycerides, apo-B, apo-C-III3, and apo-E were 2.5 +/- 0.3 micrograms/mg and 33 +/- 5, 24 +/- 3, and 162 +/- 32 ng/mg cell protein per h, respectively. On gel permeation chromatography and density gradient ultracentrifugation, the majority of apoproteins in media were found to be associated with very low density lipoproteins (VLDL) and very little eluted or sedimented with albumin. Incubations in the presence of 50-800 microU/ml of insulin resulted in dose-dependent decreases of triglyceride, phospholipid, apo-B, and apo-E accumulation in the media, paralleled by increases in the cellular contents of these lipoprotein components. The inhibitory effects of insulin on secretion were reversible. Levels of apo-C-III3 and albumin were not affected by insulin. In addition to decreasing secretory rates, the proportion of apo-B, apo-E, and apo-C-III3 associated with VLDL also decreased after the addition of insulin. Concomitantly, the proportion of apo-B eluting with LDL and apo-C-III3, and apo-E eluting near albumin increased. Control experiments, in which exogenous 125I-VLDL or endogenously labeled [14C]VLDL were added to cultures, revealed that the insulin-induced differences in VLDL accumulation and the lipid association of media apoproteins were not due to differences in the processing of VLDL by cells cultured in the presence or absence of insulin. Therefore, it appears that insulin may inhibit the secretion of VLDL perhaps by reducing the intracellular association of lipids and apoproteins.
Detection of Mutations in<i>EGFR</i>in Circulating Lung-Cancer Cells
Authors: Shyamala Maheswaran, Lecia V. Sequist, Sunitha Nagrath, Lindsey Ulkus, Brian Brannigan, Chey V. Collura, Elizabeth Inserra, Sven Diederichs, A. John Iafrate, Daphne W. Bell, Subba Digumarthy, Alona Muzikansky, Daniel Irimia, Jeffrey Settleman, Ronald G. Tompkins, Thomas J. Lynch, Mehmet Toner, Daniel A. Haber
Journal: New England Journal of Medicine (2008)

The use of tyrosine kinase inhibitors to target the epidermal growth factor receptor gene (EGFR) in patients with non-small-cell lung cancer is effective but limited by the emergence of drug-resistance mutations. Molecular characterization of circulating tumor cells may provide a strategy for noninvasive serial monitoring of tumor genotypes during treatment.We captured highly purified circulating tumor cells from the blood of patients with non-small-cell lung cancer using a microfluidic device containing microposts coated with antibodies against epithelial cells. We performed EGFR mutational analysis on DNA recovered from circulating tumor cells using allele-specific polymerase-chain-reaction amplification and compared the results with those from concurrently isolated free plasma DNA and from the original tumor-biopsy specimens.We isolated circulating tumor cells from 27 patients with metastatic non-small-cell lung cancer (median number, 74 cells per milliliter). We identified the expected EGFR activating mutation in circulating tumor cells from 11 of 12 patients (92%) and in matched free plasma DNA from 4 of 12 patients (33%) (P=0.009). We detected the T790M mutation, which confers drug resistance, in circulating tumor cells collected from patients with EGFR mutations who had received tyrosine kinase inhibitors. When T790M was detectable in pretreatment tumor-biopsy specimens, the presence of the mutation correlated with reduced progression-free survival (7.7 months vs. 16.5 months, P<0.001). Serial analysis of circulating tumor cells showed that a reduction in the number of captured cells was associated with a radiographic tumor response; an increase in the number of cells was associated with tumor progression, with the emergence of additional EGFR mutations in some cases.Molecular analysis of circulating tumor cells from the blood of patients with lung cancer offers the possibility of monitoring changes in epithelial tumor genotypes during the course of treatment.
Mechanism of the serotonin effect on lung transvascular fluid and protein movement in awake sheep.
Authors: K L Brigham, P J Owen
Journal: Circulation Research (1975)

To see how serotonin affects filtration from lung vessels, we measured vascular pressures, lung lymph flow, lung lymph and blood plasma protein concentrations, arterial blood gases, cardiac output, and lung water content in unanesthetized sheep before and during intravenous serotonin infusions and compared serotonin effects with the effects of inflating a balloon in the left atrium in the same sheep. Serotonin caused a dose-related increase in lung lymph flow and a dose-related decrease in lymph-plasma protein concentration ratios. Steady-state 4-hour serotonin infusions at 4 mu-g/kg min-1 caused lymph flow to increase from 5.4 plus or minus 0.7 (SE) ml/hour to 8.3 plus or minus 1.3 ml/hour, lymph-plasma albumin ratios to fall from 0.78 plus or minus 0.05 to 0.72 plus or minus 0.04, lymph-plasma globulin ratios to fall from 0.64 plus or minus to 0.56 plus or minus 0.02, and pulmonary arterial and left atrial pressures to increase by 3 cm H-20 each. Lymph clearance and permeability-surface area products for eight protein fractions ranging from 36 A to 96 A in molecular radius during steady-state serotonin infusion studies were not significantly different from those during steady-state increased pressure studies. Four-hour infusions of serotonin at 4 mu-g/kg/kg min-1 caused a moderate fall in arterial Po-2 and a slight increase in arterial pH but did not affect cardiac output or cause pulmonary edema. We conclude that serotonin increases lung transvascular filtration primarily by increasing the transmural pressure gradient in exchanging vessels rather than by increasing vascular permeability.
Prognostic value of thallium-201 myocardial perfusion imaging. A diagnostic tool comes of age.
Authors: K A Brown
Journal: Circulation (1991)

D uring the past 10 years, the use of thallium- 201 myocardial perfusion imaging has un- dergone considerable expansion and evalu- ation.Originally conceived as a noninvasive diagnostic tool useful in determining the presence or absence of anatomical coronary artery disease,1-4 201T1 imaging has now been shown to have important prognostic value in a wide spectrum of patients with coronary artery disease.5-49This prognostic value derives from the ability of 201T1 imaging to identify the presence and extent of jeopardized viable myocar- dium.After a brief background discussion, data are reviewed that concern the prognostic value of 201T1 imaging in three primary populations-1) patients presenting with known or suspected coronary artery disease, 2) post-myocardial infarction patients, and 3) patients undergoing noncardiac surgery.Data comparing the prognostic value of 201T1 predictors to other patient variables, including clinical, electrocar- diographic, and angiographic variables, are dis- cussed.Finally, the physiological basis of these ob- servations are examined.
Inflammation control gets fishy
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

A new study explains how a diet high in oily fish like salmon and mackerel improves inflammatory conditions, particularly in combination with low doses of aspirin. On page 713, Arita et al. decipher the structure of an antiinflammatory lipid in humans that is derived from an essential fatty acid in fish oil.
Delamanid improves outcomes and reduces mortality in multidrug-resistant tuberculosis
Authors: Vija Skripconoka, Manfred Danilovits, Lea Pehme, Tarmo Tomson, Girts Skenders, Tiina Kummik, Andra Cirule, Vaira Leimane, Anu Kurve, Klavdia Levina, Lawrence J. Geiter, Davide Manissero, Charles D. Wells
Journal: European Respiratory Journal (2012)

Multidrug-resistant and extensively drug-resistant tuberculosis (TB) are associated with worse treatment outcomes for patients, including higher mortality, than for drug-sensitive tuberculosis. Delamanid (OPC-67683) is a novel anti-TB medication with demonstrated activity against multidrug-resistant disease. Patients who participated in the previously reported randomised, placebo-controlled trial of delamanid and the subsequent open-label extension trial were eligible to participate in a 24-month observational study designed to capture treatment outcomes. Treatment outcomes, as assessed by clinicians and defined by the World Health Organization, were categorised as favourable and unfavourable. Delamanid treatment groups were combined for analysis, based on their duration of treatment. In total, for 421 (87.5%) out of 481 patients from the original randomised controlled trial, consent was granted for follow-up assessments. Favourable outcomes were observed in 143 (74.5%) out of 192 patients who received delamanid for ≥6 months, compared to 126 (55%) out of 229 patients who received delamanid for ≤2 months. Mortality was reduced to 1.0% among those receiving long-term delamanid versus short-term/no delamanid (8.3%; p&lt;0.001). Treatment benefit was also seen among patients with extensively drug-resistant TB. This analysis suggests that treatment with delamanid for 6 months in combination with an optimised background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant TB.
Relationship Between Tumor and Plasma Levels of hTERT mRNA in Patients with Colorectal Cancer: Implications for Monitoring of Neoplastic Disease
Authors: Liliana Terrin, Enrica Rampazzo, Salvatore Pucciarelli, Marco Agostini, Roberta Bertorelle, Giovanni Esposito, Paola DelBianco, Donato Nitti, Anita De Rossi
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Colorectal cancer (CRC) is one of the most common cancers in western countries. Identification of circulating markers for CRC would optimize early stage diagnosis and the monitoring for disease recurrence. Expression of telomerase reverse transcriptase (hTERT) is essential to the oncogenic process and might be used as a molecular marker of neoplastic disease. Experimental Design: Eighty-five CRC samples (25 stage I, 15 stage II, 15 stage III, and 30 stage IV), the available corresponding noncancerous mucosa (n = 42), and plasma collected at the time of surgery (n = 49) were analyzed. Control plasma samples were obtained from 43 age-matched healthy subjects. All hTERT transcripts (hTERT-AT) and transcripts encoding the functional protein (hTERT-FL) were quantified by real-time PCR. Results: hTERT-AT was found to correlate with hTERT-FL (r = 0.849; P &amp;lt; 0.0001) mRNA levels in tumors. Both hTERT mRNAs were significantly higher in tumors than in adjacent noncancerous mucosa and both significantly increased with tumor progression (P &amp;lt; 0.0001). In contrast to controls, all but two plasma samples from CRC patients were positive for hTERT mRNAs. Using the cutoff value of 180 copies hTERT-AT/mL, the sensitivity and specificity of the assay for CRC detection were 92% and 100%, respectively. Furthermore, hTERT-AT mRNA levels in plasma significantly correlated with hTERT-AT mRNA levels in tumors (r = 0.702, P &amp;lt; 0.0001). Conclusions: These findings indicate that quantification of hTERT mRNA in plasma may be used as a marker for detection and monitoring of neoplastic colorectal disease.
Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages
Authors: Noriyuki Ouchi, Shinji Kihara, Yukio Arita, Makoto Nishida, Akifumi Matsuyama, Yoshihisa Okamoto, Masato Ishigami, Hiroshi Kuriyama, Ken Kishida, Hitoshi Nishizawa, Kikuko Hotta, Masahiro Muraguchi, Yasukazu Ohmoto, Shizuya Yamashita, Tohru Funahashi, Yuji Matsuzawa
Journal: Circulation (2001)

Background —Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery disease. We previously demonstrated that adiponectin acts as a modulator for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. Methods and Results —Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern and immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry. Conclusions —The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.
Progesterone treatment in chylothorax associated with pulmonary tuberous sclerosis
Authors: V Jounieaux, S Druelle, I Mayeux, E Grimault, JC Charet
Journal: European Respiratory Journal (1996)

We report the case of a young woman with tuberous sclerosis who developed a chylous pleural effusion after several invasive procedures for treatment of recurring pneumothoraces. Oophorectomy was rejected by the patient and progesterone therapy initiated. Medroxyprogesterone acetate administration led to a complete disappearance of the chylothorax in 8 months. The patient was kept on therapy, and no recurrence of pleural effusion has been observed up to the present (22 months follow-up). However, a progressive deterioration in pulmonary function was observed, with a significant decrease in pulmonary transfer factor and increase in airway obstruction. In conclusion, this report demonstrates an objective benefit of progesterone therapy on chylous effusion associated with pulmonary tuberous sclerosis.
Planar cell polarity genes control the connectivity of enteric neurons
Authors: Valentina Sasselli, Werend Boesmans, Pieter Vanden Berghe, Fadel Tissir, André M. Goffinet, Vassilis Pachnis
Journal: Journal of Clinical Investigation (2013)

A highly complex network of intrinsic enteric neurons is required for the digestive and homeostatic functions of the gut. Nevertheless, the genetic and molecular mechanisms that regulate their assembly into functional neuronal circuits are currently unknown. Here we report that the planar cell polarity (PCP) genes Celsr3 and Fzd3 are required during murine embryogenesis to specifically control the guidance and growth of enteric neuronal projections relative to the longitudinal and radial gut axes. Ablation of these genes disrupts the normal organization of nascent neuronal projections, leading to subtle changes of axonal tract configuration in the mature enteric nervous system (ENS), but profound abnormalities in gastrointestinal motility. Our data argue that PCP-dependent modules of connectivity established at early stages of enteric neurogenesis control gastrointestinal function in adult animals and provide the first evidence that developmental deficits in ENS wiring may contribute to the pathogenesis of idiopathic bowel disorders.
Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial
Authors: David Neal Franz, Elena Belousova, Steven Sparagana, E Martina Bebin, Michael Frost, Rachel Kuperman, Olaf Witt, Michael H Kohrman, J Robert Flamini, Joyce Y Wu, Paolo Curatolo, Petrus J de Vries, Vicky H Whittemore, Elizabeth A Thiele, James P Ford, Gaurav Shah, Helene Cauwel, David Lebwohl, Tarek Sahmoud, Sergiusz Jozwiak
Journal: The Lancet (2012)
For and against: No consent should be needed for using leftover body material for scientific purposes * For * Against
Authors: P. J van Diest
Journal: BMJ (2002)

<i>Papers</i> p 634 <i>In Britain the Alder Hey scandal brought to public attention the fact that body material left over after diagnostic procedures may be used for teaching and research—usually without the patient9s consent. Paul van Diest argues that, Alder Hey apart, this practice has not caused protest, mainly because the alternative would be to discard the material. He argues that self determination is not an overriding principle in the case of material that is otherwise thrown away. Julian Savulescu, however, cites cases where patients have felt “used” when their tissue has been kept without their consent. He argues that the best way to retain tissue for research is through educating and encouraging people to donate their redundant tissues, not by taking them without their knowledge</i>
Lymphatic Mapping and Sentinel Lymph Node Biopsy in Women With Squamous Cell Carcinoma of the Vulva: A Gynecologic Oncology Group Study
Authors: Charles F. Levenback, Shamshad Ali, Robert L. Coleman, Michael A. Gold, Jeffrey M. Fowler, Patricia L. Judson, Maria C. Bell, Koen De Geest, Nick M. Spirtos, Ronald K. Potkul, Mario M. Leitao, Jamie N. Bakkum-Gamez, Emma C. Rossi, Samuel S. Lentz, James J. Burke, Linda Van Le, Cornelia L. Trimble
Journal: Journal of Clinical Oncology (2012)

To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer.Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed.In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%).Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva.
Prophylactic Catheter Ablation for the Prevention of Defibrillator Therapy
Authors: Vivek Y. Reddy, Matthew R. Reynolds, Petr Neuzil, Allison W. Richardson, Milos Taborsky, Krit Jongnarangsin, Stepan Kralovec, Lucie Sediva, Jeremy N. Ruskin, Mark E. Josephson
Journal: New England Journal of Medicine (2007)

For patients who have a ventricular tachyarrhythmic event, implantable cardioverter-defibrillators (ICDs) are a mainstay of therapy to prevent sudden death. However, ICD shocks are painful, can result in clinical depression, and do not offer complete protection against death from arrhythmia. We designed this randomized trial to examine whether prophylactic radiofrequency catheter ablation of arrhythmogenic ventricular tissue would reduce the incidence of ICD therapy.Eligible patients with a history of a myocardial infarction underwent defibrillator implantation for spontaneous ventricular tachycardia or fibrillation. The patients did not receive antiarrhythmic drugs. Patients were randomly assigned to defibrillator implantation alone or defibrillator implantation with adjunctive catheter ablation (64 patients in each group). Ablation was performed with the use of a substrate-based approach in which the myocardial scar is mapped and ablated while the heart remains predominantly in sinus rhythm. The primary end point was survival free from any appropriate ICD therapy.The mortality rate 30 days after ablation was zero, and there were no significant changes in ventricular function or functional class during the mean (+/-SD) follow-up period of 22.5+/-5.5 months. Twenty-one patients assigned to defibrillator implantation alone (33%) and eight patients assigned to defibrillator implantation plus ablation (12%) received appropriate ICD therapy (antitachycardia pacing or shocks) (hazard ratio in the ablation group, 0.35; 95% confidence interval, 0.15 to 0.78, P=0.007). Among these patients, 20 in the control group (31%) and 6 in the ablation group (9%) received shocks (P=0.003). Mortality was not increased in the group assigned to ablation as compared with the control group (9% vs. 17%, P=0.29).In this randomized trial, prophylactic substrate-based catheter ablation reduced the incidence of ICD therapy in patients with a history of myocardial infarction who received ICDs for the secondary prevention of sudden death. (Current Controlled Trials number, ISRCTN62488166 [controlled-trials.com].).
Psychiatry in Viet Nam-1966
Authors: ROBERT A. McKINLEY
Journal: American Journal of Psychiatry (1966)

There is a real place for the visiting psychiatrist in Viet Nam, even though his period of duty may be as short as two months. Psychiatric facilities in the country are few and seriously undermanned, but the staff at the major mental hospital in Bien Hoa is remarkable for its dedication to the patients. Besides reporting on the Bien Hoa and other hospitals, the author describes Vietnamese views about mental illness and its treatment.