tbuckley/cabot-search huggingface dataset:
Estrogen Prevents Oxidative Stress–Induced Endothelial Cell Apoptosis in Rats
Authors: Noriko Sudoh, Kenji Toba, Masahiro Akishita, Junya Ako, Masayoshi Hashimoto, Katsuya Iijima, Seungbum Kim, Yi-Qiang Liang, Yumiko Ohike, Tokumitsu Watanabe, Ieharu Yamazaki, Masao Yoshizumi, Masato Eto, Yasuyoshi Ouchi
Journal: Circulation (2001)

Background —Estrogen replacement attenuates the increased risk of cardiovascular disease in postmenopausal women. Recent studies using an in vitro culture system have shown that estrogen inhibits endothelial cell (EC) apoptosis. The in vivo relevance of this finding, however, is not defined. To do so, we have developed a rat vascular injury model in which EC apoptosis induced by hydrogen peroxide plays a role. Methods and Results —Intracarotid arterial administration of 0.01 mmol/L hydrogen peroxide for 5 minutes evoked EC apoptosis after 6 to 24 hours, determined by nuclear staining with Hoechst 33342, terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling, and electron microscopy. Apoptosis was associated with EC loss and was followed by EC regeneration at 72 hours and neointima formation at 1 to 2 weeks. Estradiol replacement in ovariectomized female Wistar rats decreased the rate of apoptotic ECs by ≈50%, assayed by nuclear morphology of en face specimens, resulting in increased remaining ECs and decreased neointima formation. Progesterone did not influence the effects of estradiol on EC apoptosis. Conclusions —These results provide new insight into the cardioprotective action of estrogen as well as a paradigm of the response-to-injury hypothesis.
Abstract 2015: BRCA1 expression and genomic aberrations in triple negative breast tumors.
Authors: Teresa Tapia, Andrés Aravena, Carolina Alvarez, Valeria Cornejo, Wanda Fernandez, Mauricio Camus, Alejandro Maass, Pilar Carvallo
Journal: Cancer Research (2013)

Abstract Among breast cancer tumors, a group named as triple-negative breast cancer (TNBC) which do not express hormone receptors and HER2 (ER-, PR-, HER2-) do not have specific therapy. Therefore, knowing the genes involved in this type of tumor is highly relevant for treatment. Intense research in these tumors has been performed in order to identify new targets. We studied 48 TNBC tumors from Chilean patients by different approaches. In these tumors, we determined the expression, by immunohistochemistry, the different cytokeratins (CK5, CK14, and CK8/18) and EGFR. In addition, we analyzed BRCA1 expression and localization by immunohistochemistry. Using array-CGH, we characterized the genomic aberrations, in order to identify common alterations between tumors. A 62.5% (30/48) of the tumors were classified as basal-like. Expression and localization of BRCA1 analysis revealed that a 22.9% (11/48) of tumors presented normal expression of nuclear BRCA1, a 29.2% (14/48) has low or absent nuclear expression and a 47.9% (23/48) has altered BRCA1 localization, in addition to low expression in some cases. This suggests that the loss of expression of BRCA1 or its altered localization may be relevant for tumor progression. Analysis of genomic alterations by array-CGH revealed regions of gain (4p16.3-p16.2, 7p22.3-p22.2, 11p15.5, 19p13.3) and deleted regions (1q21.1, 6p11.2; 11q22.3) shared by more than 30% of these tumors. By grouping these tumors we identified three main groups, one of which correlates with the low expression / miss-localization of BRCA1. An analysis of the genes contained in these regions can determine the signaling pathways relevant to the progression of breast cancer. In this regard, by clustering, we identified a group of TNBC tumors (17/48) with amplification of AKT1, which may be relevant as a therapeutic target. FONDECYT 1080595, CONICYT 24091058. Citation Format: Teresa Tapia, Andrés Aravena, Carolina Alvarez, Valeria Cornejo, Wanda Fernandez, Mauricio Camus, Alejandro Maass, Pilar Carvallo. BRCA1 expression and genomic aberrations in triple negative breast tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2015. doi:10.1158/1538-7445.AM2013-2015
Morphological and functional restoration of parietal cells in Helicobacter pylori associated enlarged fold gastritis after eradication
Authors: Y Murayama, J Miyagawa, Y Shinomura, S Kanayama, Y Yasunaga, H Nishibayashi, K Yamamori, Y Higashimoto, Y Matsuzawa
Journal: Gut (1999)

Helicobacter pylori infections are associated with hypochlorhydria in patients with pangastritis. It has previously been shown that eradication of H pylori leads to an increase in acid secretion in H pylori associated enlarged fold gastritis, suggesting that H pylori infection affects parietal cell function in the gastric body. The aim of this study was to evaluate the effects of H pylori infection on parietal cell morphology and function in hypochlorhydric patients.The presence of H pylori infection, mucosal length, and inflammatory infiltration were investigated in six patients with enlarged fold gastritis and 12 patients without enlarged folds. Parietal cell morphology was examined by immunohistochemistry using an antibody against the alpha subunit of H(+),K(+)-ATPase and electron microscopy. In addition, gastric acid secretion and fasting serum gastrin concentration were determined before and after the eradication of H pylori.In the H pylori positive patients with enlarged fold gastritis, fold width, foveolar length, and inflammatory infiltration were increased. In addition, the immunostaining pattern of H(+), K(+)-ATPase was less uniform, and the percentage of altered parietal cells showing dilated canaliculi with vacuole-like structures and few short microvilli was greatly increased compared with that in H pylori positive patients without enlarged folds. After eradication, fold width, foveolar length, and inflammatory infiltrates decreased and nearly all parietal cells were restored to normal morphology. On the other hand, altered parietal cells were negligible in H pylori negative patients. In addition, the basal acid output and tetragastrin stimulated maximal acid output increased significantly from 0.5 (0.5) to 4.1 (1.5) mmol/h and from 2.5 (1.2) to 13.8 (0.7) mmol/h (p<0.01), and fasting serum gastrin concentrations decreased significantly from 213.5 (31.6) to 70.2 (7.5) pg/ml (p<0.01) after eradication in patients with enlarged fold gastritis.The morphological changes in parietal cells associated with H pylori infection may be functionally associated with the inhibition of acid secretion seen in patients with enlarged fold gastritis.
Ophthalmology's New Tools May Have Profound Impact on Refractive Surgery
Authors: Timothy F. Kirn
Journal: JAMA (1987)

A NEW SURGICAL PROCEDURE, a growth factor, and a new laser could be a boon to ophthalmology, if their research promise holds out. Many ophthalmologists are optimistic. They hope that adding these tools to their physician's bag will improve the ophthalmic surgeon's ability to change the shape of the cornea and reduce or eliminate refractive errors. Most say that, although all three are still in the highly experimental stage, they are excited by the potential. And, they say, they think if any (or all) of the three live up to that avowed potential, it could dramatically improve refractive corneal surgery, a field that George O. Waring III, MD, chief of refractive surgery at Emory University School of Medicine, Atlanta, and director of the Prospective Evaluation of Radial Keratotomy (PERK) study, describes as "constantly in a state of flux, that is, change and development." Perhaps the most exciting and the most
What Is a Curriculum?
Authors: Jack Ende, Frank Davidoff
Journal: Annals of Internal Medicine (1992)

Dissatisfaction with the current internal medicine residency experience has led to proposals for various new curricula. Unfortunately, the more basic question of "What is a curriculum?" or more accurately, "What curriculum model is most appropriate for clinical training?" has remained largely unexamined. The dominant curriculum model, although valuable, may not be adequate for the task. In its place we propose an experiential model that is more congruent with the realities of graduate medical education.
Use of an indwelling catheter for examining cardiovascular responses to pericardial administration of bradykinin in rat
Authors: D. A. McDermott, S. T. Meller, G.F. Gebhart, D. D. Gutterman
Journal: Cardiovascular Research (1995)

Objective and Methods: Epicardial application of pharmacologic agonists has been used to study nociceptive and reflex responses to agents such as bradykinin. We utilized a model where intrapericardial bradykinin was administered in a closed-chest rat. The procedure allows for reproducible administration of microliter doses of pharmacologic agonists in both conscious and anesthetized animals. Results: Bradykinin (BK) has been shown to produce sympathoexcitatory reflexes when applied to the heart. BK typically produced a dose-dependent (0.001–10 μg) decrease in arterial blood pressure and tachycardia in pentobarbital-anesthetized rats. In contrast, in α-chloralose-anesthetized or awake rats, pericardial administration of BK produced a dose-dependent (0.001–10 μg) increase in arterial blood pressure and tachycardia. Maximal cardiovascular changes were produced by 1 μg BK. The maximum change in arterial pressure was +33.6 ± 9% in awake, + 38.9 ± 6% in chloralose-anesthetized, and − 20 ± 7% in pentobarbital-anesthetized rats. In α-chloralose-anesthetized rats, tachyphylaxis to pericardial administration of 1 μg BK occurred at 5 and 15, but not at 30 min dosing intervals. Administration of the receptor selective B2-antagonist d-Arg,[Hyp3,Thi5,8d-Phe7]-BK (200 μg) or the mixed B2/B1 antagonist [Thi5,8d-Phe7]-BK (200 μg), produced similar attenuation of the pressor and tachycardia responses to BK. Bilateral transection of the cervical vagus nerve, bilateral removal of the stellate ganglion or ganglion blockade (hexamethonium), but not administration of indomethacin, reduced the magnitude of the tachycardia to BK. Only ganglionic blockade significantly reduced the pressor response to BK. Conclusions: These results demonstrate that pericardial administration of BK produces a tachycardia and pressor effect in awake and α-chloralose-anesthetized rats and a tachycardia and depressor effect in pentobarbital-anesthetized rats. These responses appear to be mediated through activation of BK (presumably B2) receptors on cardiac vagal and sympathetic afferents, and may include a direct action of BK on the heart. This model of pericardial administration of pharmacologic agonists may be useful in studies of cardiac pain and reflex responses.
Why minds create gods: Devotion, deception, death, and arational decision making
Authors: Scott Atran, Ara Norenzayan
Journal: Behavioral and Brain Sciences (2004)

The evolutionary landscape that canalizes human thought and behavior into religious beliefs and practices includes naturally selected emotions, cognitive modules, and constraints on social interactions. Evolutionary by-products, including metacognitive awareness of death and possibilities for deception, further channel people into religious paths. Religion represents a community's costly commitment to a counterintuitive world of supernatural agents who manage people's existential anxieties. Religious devotion, though not an adaptation, informs all cultures and most people.
To Drink or Not to Drink?
Authors: Ira J. Goldberg
Journal: New England Journal of Medicine (2003)

A number of epidemiologic studies have found an association of alcohol intake with a reduced risk of cardiovascular disease. These observations have been purported to explain the so-called French paradox: the lower rate of cardiovascular disease in France than in its neighboring countries to the north and in the United States, despite the relatively high intake of fat in France. Several studies attribute the French paradox to the relatively high consumption of red wine by the French.1 Other epidemiologic studies,2,3 including that of Mukamal et al. in this issue of the Journal, 4 suggest that all alcoholic beverages, not wine . . .
GC1QR: A NOVEL BIOMARKER ASSOCIATED WITH RISK OF CARDIOVASCULAR EVENTS
Authors: Jeremy P. Berman, Michael Farkouh, Sanjum Sethi, Kshitij Shah, Luke Hermann, Berhane Ghebrehiwet, Rupa Iyengar, Alexander Tarasov, Rosane Nisenbaum, Shiny Mathewkutty, Lakshmi Ramanathan, Ellinor Peerschke
Journal: Journal of the American College of Cardiology (2013)
A 70 Amino Acid Region within the Semaphorin Domain Activates Specific Cellular Response of Semaphorin Family Members
Authors: Adam M Koppel, Leonard Feiner, Hiroaki Kobayashi, Jonathan A Raper
Journal: Neuron (1997)

The semaphorin family contains secreted and transmembrane signaling proteins that function in the nervous, immune, and cardiovascular systems. Chick collapsin-1 is a repellent for specific growth cones. Two other secreted members of the semaphorin family, collapsin-2 and -3, are structurally similar to collapsin-1 but have different biological activities. Semaphorins contain a 500 amino acid family signature semaphorin domain. We show in this study that (1) the semaphorin domain of collapsin-1 is both necessary and sufficient for biological activity, (2) the semaphorin domain contains a 70 amino acid region that specifies the biological activity of the three family members, and (3) the positively charged carboxy terminus potentiates activity without affecting specificity. We propose that semaphorins interact with their receptors through two independent binding sites: one that mediates the biological response and one that potentiates it.
Late reactivation of resolved hepatitis B virus infection: An increasing complication post rituximab‐based regimens treatment?
Authors: Maria J. Garcia‐Rodriguez, Miguel A. Canales, Dolores Hernandez‐Maraver, Fernando Hernandez‐Navarro
Journal: American Journal of Hematology (2008)

Reactivation of hepatitis B infection is an increasing problem for patients with lymphoma, even in resolved infections, who were treated with rituximab-based regimens. Our cases point out the need of prolonged prophylaxis in HBsAg-negative patients due to the high risk of developing fatal reactivation.
Tcl1 interacts with Atm and enhances NF-κB activation in hematologic malignancies
Authors: Eugenio Gaudio, Riccardo Spizzo, Francesco Paduano, Zhenghua Luo, Alexey Efanov, Alexey Palamarchuk, Amanda S. Leber, Mohamed Kaou, Nicola Zanesi, Arianna Bottoni, Stefan Costinean, Laura Z. Rassenti, Tatsuya Nakamura, Thomas J. Kipps, Rami I. Aqeilan, Yuri Pekarsky, Francesco Trapasso, Carlo M. Croce
Journal: Blood (2011)
On the Treatment of Ovarian Dropsy by Operation
Authors: W. H. Bainbrigge
Journal: BMJ (1847)

现代社会对公共卫生体系的挑战既来自于传染病也包括慢性疾病，需要改善环境卫生、职业卫生和精神卫生状况，需要减少伤害、强化公共卫生服务体系的可及性、提高应对不可预知和突发事件，比如自然灾害和生物恐怖活动的能力。
Characterization of cadmium proteinuria in man and rat.
Authors: R R Lauwerys, A Bernard, H A Roels, J P Buchet, C Viau
Journal: Environmental Health Perspectives (1984)

In workers chronically exposed to cadmium and without signs of renal insufficiency, plasma proteins with molecular weight ranging from 11,800 to 450,000 are excreted in greater amount in urine. Increased urinary excretion of low and high molecular weight proteins can occur independently. Because of its greater stability in urine and provided a sensitive immunological technique is used, the determination of retinol-binding protein is a more practical and reliable test of proximal tubular function than beta 2-microglobulin. The evaluation of renal function of workers removed from cadmium exposure indicates that cadmium-induced renal lesions, albeit of slow progression, are not reversible when exposures ceases. In workers chronically exposed to cadmium or removed from cadmium exposure, metallothionein in urine is directly correlated with cadmium in urine but not with cadmium in blood or years of cadmium exposure. The association between cadmium in urine and metallothionein in urine is independent of the status of renal function and the intensity of current exposure to cadmium. Whereas the repeated IP injection of high doses of cadmium to rat gives rise to a mixed or tubular type proteinuria, the prolonged oral administration of cadmium results mainly in the development of a glomerular type proteinuria. The former is usually reversible after cessation of treatment whereas the latter is not. Circulating antiglomerular basement membrane antibodies have been found in man and in rat chronically exposed to cadmium. The pathogenic significance of this finding deserves further investigation.
Effects of Growth Hormone Supplementation on Left Ventricular Morphology and Myocyte Function With the Development of Congestive Heart Failure
Authors: Ward V. Houck, Lydia C. Pan, Scott B. Kribbs, Mark J. Clair, George M. McDaniel, R. Stephen Krombach, William M. Merritt, Christine Pirie, Julie P. Iannini, Rupak Mukherjee, Francis G. Spinale
Journal: Circulation (1999)

Background —Release of growth hormone (GH), putatively through alterations in insulin growth factor-1 (IGF-1) levels, has been implicated to influence left ventricular (LV) myocardial structure and function. The objective of this study was to determine contributory mechanisms by which GH supplementation may influence LV function with the development of congestive heart failure (CHF). Methods and Results —Pigs were assigned to the following groups: (1) chronic pacing at 240 bpm for 3 weeks (n=10), (2) chronic pacing and GH supplementation (200 μg · kg −1 · d −1 , n=10), and (3) controls (n=8). GH treatment increased IGF-1 plasma levels by nearly 2.5-fold throughout the pacing protocol. In the untreated pacing CHF group, LV fractional shortening was reduced and peak wall stress increased. In the pacing CHF and GH groups, LV fractional shortening was higher and LV wall stress lower than untreated CHF values. Steady-state myocyte velocity of shortening was reduced with pacing CHF and was unchanged from CHF values with GH treatment. In the presence of 25 nmol/L isoproterenol, the change in myocyte shortening velocity was reduced in the untreated CHF group and increased in the GH-treated group. LV sarcoplasmic reticulum Ca 2+ -ATPase abundance was reduced with pacing CHF but was normalized with GH treatment. Conclusions —Short-term GH supplementation improved LV pump function in pacing CHF as a result of favorable effects on LV remodeling and contractile processes. Thus, GH supplementation may serve as a novel therapeutic modality in developing CHF.
Distributed Network Actions by Nicotine Increase the Threshold for Spike-Timing-Dependent Plasticity in Prefrontal Cortex
Authors: Jonathan J. Couey, Rhiannon M. Meredith, Sabine Spijker, Rogier B. Poorthuis, August B. Smit, Arjen B. Brussaard, Huibert D. Mansvelder
Journal: Neuron (2007)
Road deaths three times higher in poorer European countries
Authors: Z. Kmietowicz
Journal: BMJ (2009)

Countries in the World Bank’s Europe and central Asia region need to develop a systematic response to improve road safety, to protect the health and economic wellbeing of their citizens, says a report, Confronting “Death on Wheels” Making Roads Safe in Europe and Central Asia .

Several factors have contributed to rapid increases of deaths and injuries from road traffic incidents in these countries, which include the Commonwealth of Independent States (countries of the former Society Union), eastern and central Europe, the Baltics, and the Balkans, it says. These include weak road safety management capacity, deteriorated roads, unsafe vehicles, poor driver behaviour, patchy enforcement of road safety …
Mutations in<i>GNA11</i>in Uveal Melanoma
Authors: Catherine D. Van Raamsdonk, Klaus G. Griewank, Michelle B. Crosby, Maria C. Garrido, Swapna Vemula, Thomas Wiesner, Anna C. Obenauf, Werner Wackernagel, Gary Green, Nancy Bouvier, M. Mert Sozen, Gail Baimukanova, Ritu Roy, Adriana Heguy, Igor Dolgalev, Raya Khanin, Klaus Busam, Michael R. Speicher, Joan O'Brien, Boris C. Bastian
Journal: New England Journal of Medicine (2010)

Uveal melanoma is the most common intraocular cancer. There are no effective therapies for metastatic disease. Mutations in GNAQ, the gene encoding an alpha subunit of heterotrimeric G proteins, are found in 40% of uveal melanomas.
P180Notch-dependent regulation of endothelial-to-mesenchimal transition is impaired in aortic endothelial cells of BAV patients
Authors: AS Kostina, ND Gavriliuk, VE Uspensky, OB Irtiuga, OM Moiseeva, AA Kostareva
Journal: Cardiovascular Research (2014)

Purpose: Endothelial-to- mesenchimal transition (EndoMT) is an important process for cardiac outflow tract and aortic valve formation. Notch signaling is known as one of the regulators of EndoMT in development but its role in regulation of human heart development remains obscure due to difficulties of studying human development. It has been shown in our as well as other previous studies, that patents with defects of left ventricular outflow tract may have mutations in Notch1 gene as well as in other genes of Notch pathway. Thus, it has been supposed that a dysfunction in Notch pathway could lead to mistakes in development leading to malformations of LVOT, in particular, to BAV. In this study we recapitulated early cardiac development by inducing EndoMT in human endothelial aortic cells (HAEC).The purpose of this study was to compare the efficiency of Notch-dependent EndoMT in aortic endothelium of BAV patients and healthy donors. Methods: HAEC were isolated from tissue fragments of BAV-associated thoracic aortic aneurysm patients after surgery and from healthy donors. EndoMT was induced by different stimuli: 1) TGFβ; 2) NICD (activated domain of Notch1; 3) Notch ligands – Dll1, Dll4, Jag1, Jag2. Effectiveness of EndoMT was estimated by loss of endothelial and gain of mesenchimal markers by immunocytochemistry and qPCR. Results: We studied EndoMT induction in control and TAA-BAV group. We show that the extent of EndoMT induction in aortic endothelial cells is strongly dependent on stimuli used: the strongest inducer was TGFFβ. However HAEC co-culture with the cells bearing Notch ligands Dll1, Dll4, Jag1, Jag2 also lead to the induction of EndoMT. Finally we observed the differences in the extent of EndoMT induction between the HAEC of healthy donors and HAEC from TAA-BAV patients: NICD induced EndoMT in HAEC of patients less efficiently comparing to normal cells. Conclusions: We developed an effective in vitro system which allows studying EndoM directly using the patients' primary cells (HAEC) thus recapitulating processes seen in early cardiogenesis. Our results provide evidence that Notch-dependent EndoMT regulation is impaired in HAEC of BAV patients. Our results for the first time directly confirm the hypothesis that Notch pathway disruption could be responsible for LVOT malformations and, in particular, may lead to BAV.
Memorial to Sir Walter Fletcher
Authors: S. Baldwin, F. G. Hopkins, None D'Abernon, C. S. Sherrington, A. Gregg, H. J. Waring, C. J. Martin, T. R. Elliott, R. Muir, H. Chick, G. M. Trevelyan, M. R. James, A. E. Boycott, H. H. Dale, E. Mellanby
Journal: BMJ (1934)