tbuckley/cabot-search huggingface dataset:
Incorporation of intravenously injected albumin, immunoglobulin G, and fibrinogen in guinea pig megakaryocyte granules.
Authors: P J Handagama, M A Shuman, D F Bainton
Journal: Journal of Clinical Investigation (1989)

In a previous study we provide evidence for a circuitous pathway by which circulating plasma proteins enter megakaryocyte granules by an endocytic mechanism and are returned to the circulation in platelets (1987. Proc. Natl. Acad. Sci. USA. 84:861-865). Horseradish peroxidase (40,000 mol wt) was injected into guinea pigs and its uptake into megakaryocyte organelles examined by electron microscopy and cytochemistry. In the present study we tested the ability of guinea pig megakaryocytes to take up intravenously injected albumin, IgG, and fibrinogen. We used two types of proteins to study the endocytic pathway: (a) heterologous human proteins, which were detected immunohistochemically using antibodies that do not crossreact with the native guinea pig counterparts; and (b) human and guinea pig proteins labeled with the small (250 mol wt), inert molecule, biotin, which were detected using an antibody against biotin. We detected all three of the injected proteins in bone marrow megakaryocytes in patterns identical to those of native counterparts. The injected protein consistently appeared in platelets 24 h later and was secreted in response to thrombin. We conclude that there are at least two mechanisms by which guinea pig megakaryocyte granules acquire proteins (a) endogenous synthesis, as demonstrated by others, and (b) endocytosis of plasma proteins synthesized by other types of cells.
Oestrogen receptors and breast cancer
Authors: R. M Elledge, C K. Osborne
Journal: BMJ (1997)

Breast cancer is marked by great clinical and biological diversity. Some women can be cured, while others die rapidly over just a few months. Systemic treatments can have gratifying and possibly curative effects for some, while for others they add only misery and financial hardship. Given this great heterogeneity, are women with breast cancer best served by therapeutic approaches emphasising homogeneity or ones that reflect the variability of the disease in individual choices of treatment? A case in point is the use of oestrogen receptor status in making decisions about endocrine therapy.

Oestrogen receptors are required for oestrogen stimulated growth and proliferation of breast cancer. They are found to some degree in 50-80% of breast tumours. Endocrine treatments are designed to antagonise the effects of oestrogen. Oophorectomy, luteinising hormone releasing hormone agonists, and aromatase inhibition all reduce the level of oestrogen, while antioestrogens such as tamoxifen competitively block binding of oestrogen to receptors and thus antagonise transcriptional activation of genes required for tumour growth.

Twenty five years ago it was first hypothesised that the response to such endocrine treatments would depend on the presence of oestrogen receptors in the tumours. And indeed, 50-60% of receptor positive metastatic tumours do respond.1 For tumours that test negative for oestrogen and progesterone receptors, the response rate (in terms of tumour …
Increased urinary leukotriene E<sub>4</sub>excretion in patients with atopic dermatitis
Authors: T. Hishinuma, N. Suzuki, S. Aiba, H. Tagami, M. Mizugaki
Journal: British Journal of Dermatology (2001)

Background Synthesis of cysteinyl leukotrienes (LTs) is known to play a part in the pathogenesis of inflammatory diseases. Objectives To define the involvement of cysteinyl LTs in atopic dermatitis (AD). Methods Synthesis of cysteinyl LTs was assessed in patients with AD and healthy volunteers by measuring urinary LTE4, a useful index of systemic cysteinyl LT synthesis, using liquid chromatography/tandem mass spectrometry. Results Mean ± SD urinary LTE4 levels in patients with AD (125 ± 69 pg mg−1 creatinine, n = 20) were significantly higher (P < 0·01) than in healthy volunteers (60 ± 19 pg mg−1 creatinine, n = 17). A significant correlation between urinary LTE4 and total serum IgE levels in patients with AD was observed (r = 0·643, P < 0·05). Conclusions Our findings demonstrate an enhanced synthesis of cysteinyl LTs in patients with AD and suggest that cysteinyl LTs are involved in the pathophysiology of AD.
H+/solute-induced intracellular acidification leads to selective activation of apical Na+/H+ exchange in human intestinal epithelial cells
Authors: David T. Thwaites, Dianne Ford, Michael Glanville, Nicholas L. Simmons
Journal: Journal of Clinical Investigation (1999)

The intestinal absorption of many nutrients and drug molecules is mediated by ion-driven transport mechanisms in the intestinal enterocyte plasma membrane. Clearly, the establishment and maintenance of the driving forces — transepithelial ion gradients — are vital for maximum nutrient absorption. The purpose of this study was to determine the nature of intracellular pH (pHi) regulation in response to H+-coupled transport at the apical membrane of human intestinal epithelial Caco-2 cells. Using isoform-specific primers, mRNA transcripts of the Na+/H+ exchangers NHE1, NHE2, and NHE3 were detected by RT-PCR, and identities were confirmed by sequencing. The functional profile of Na+/H+ exchange was determined by a combination of pHi, 22Na+ influx, and EIPA inhibition experiments. Functional NHE1 and NHE3 activities were identified at the basolateral and apical membranes, respectively. H+/solute-induced acidification (using glycylsarcosine or β-alanine) led to Na+-dependent, EIPA-inhibitable pHi recovery or EIPA-inhibitable 22Na+ influx at the apical membrane only. Selective activation of apical (but not basolateral) Na+/H+ exchange by H+/solute cotransport demonstrates that coordinated activity of H+/solute symport with apical Na+/H+ exchange optimizes the efficient absorption of nutrients and Na+, while maintaining pHi and the ion gradients involved in driving transport.
Altered angiotensin II-induced activation of intracellular signalling pathways in failing human ventricular myocytes
Authors: Pietro A. Modesti, Alessandra Modesti, Simone Vanni, Thomas Toscano, Ilaria Cecioni, Tania Gamberi, Iacopo Bertolozzi, Massimo Maccherini, GianGastone Neri Serneri
Journal: Journal of the American College of Cardiology (2003)
SPECIFIC AND NON-SPECIFIC IMMUNITY IN EXPERIMENTAL CRYPTOCOCCOSIS IN MICE
Authors: Donald B. Louria
Journal: The Journal of Experimental Medicine (1960)

The course of lethal cryptococcosis in mice was modified by immunization with the same strain or different strains of Cryptococcus neoformans. Protection was associated with a definite decrease in tissue fungus multiplication over the initial 7 days of infection. Such immunity was species-specific and did not protect against heterologous challenge with Staphylococcus aureus, Klebsiella pneumoniae, or Mycobacterium tuberculosis. Similar modification of lethal cryptococcosis was produced by intraperitoneal inoculation of 100 to 200 microg. of Salmonella endotoxin 7 days prior to challenge. In non-specifically (endotoxin) immunized mice there was only a minimal reduction in tissue cryptococcus census during the 1st week of infection. When small numbers of virulent cryptococci were injected intravenously into normal mice, tissue populations rose markedly in all organs studies during the first 7 days. A progressive fall in tissue fungus census was then observed in most mice during the next 6 months. The increase in resistance to cryptococcal challenge following specific immunization, the non-specific protection conferred by injection of bacterial endotoxin and the ability to control and eventually reduce infections with small inocula may well be dependent in each case on the development of specific antibody.
Long-Term Safety and Effectiveness of Unprotected Left Main Coronary Stenting With Drug-Eluting Stents Compared With Bare-Metal Stents
Authors: Young-Hak Kim, Duk-Woo Park, Seung-Whan Lee, Sung-Cheol Yun, Cheol Whan Lee, Myeong-Ki Hong, Seong-Wook Park, Ki Bae Seung, Hyeon-Cheol Gwon, Myung-Ho Jeong, Yangsoo Jang, Hyo-Soo Kim, In-Whan Seong, Hun Sik Park, Taehoon Ahn, In-Ho Chae, Seung-Jea Tahk, Wook-Sung Chung, Seung-Jung Park
Journal: Circulation (2009)

Limited information is available on long-term outcomes for patients with unprotected left main coronary artery disease who received drug-eluting stents (DES).In the multicenter registry evaluating outcomes among patients with unprotected left main coronary artery stenosis undergoing stenting with either bare metal stents (BMS) or DES, 1217 consecutive patients were divided into 2 groups: 353 who received only BMS and 864 who received at least 1 DES. The 3-year outcomes were compared by use of the adjustment of inverse-probability-of-treatment-weighted method. Patients receiving DES were older and had a higher prevalence of diabetes mellitus, hypertension, hyperlipidemia, and multivessel disease. In the overall population, with the use of DES, the 3-year adjusted risk of death (8.0% versus 9.5%; hazard ratio, 0.71; 95% confidence interval, 0.36 to 1.40; P=0.976) or death or myocardial infarction (14.3% versus 14.9%; hazard ratio, 0.83; 95% confidence interval, 0.49 to 1.40; P=0.479) was similar compared with BMS. However, the risk of target lesion revascularization was significantly lower with the use of DES than BMS (5.4% versus 12.1%; hazard ratio, 0.40; 95% confidence interval, 0.22 to 0.73; P=0.003). When patients were classified according to lesion location, DES was still associated with lower risk of target lesion revascularization in patients with bifurcation (6.9% versus 16.3%; hazard ratio, 0.38; 95% confidence interval, 0.18 to 0.78; P=0.009) or nonbifurcation (3.4% versus 10.3%; hazard ratio, 0.39; 95% confidence interval, 0.17 to 0.88; P=0.024) lesions with a comparable risk of death or myocardial infarction.Compared with BMS, DES was associated with a reduction in the need for repeat revascularization without increasing the risk of death or myocardial infarction for patients with unprotected left main coronary artery stenosis.
Ronald Charles King
Authors: D. King
Journal: BMJ (2014)

After house jobs at Barts, and two years as a demonstrator in physiology at the medical school, Ronald Charles King (“Ronnie”) spent a year as instructor and research assistant in gastrointestinal medicine at the University Hospital, Ann Arbor, Michigan, USA, where he was present when a flexible glass gastroscope was used to visualise the interior of the duodenum for the first time. After further posts at the old Metropolitan Hospital and back at Barts, he was appointed a consultant in general medicine at the Kent and Sussex Hospital, Tunbridge Wells. While always championing the role of the general physician in the district general hospital, he also developed interests in diabetes, gastroenterology, and, later, …
Central Pulmonary Artery Lesions in Chronic Obstructive Pulmonary Disease
Authors: Aldo Russo, Massimo De Luca, Carlo Vigna, None Vincenzo De Rito, Michele Pacilli, Antonella Lombardo, Michele Armillotta, Raffaele Fanelli, Francesco Loperfido
Journal: Circulation (1999)

Background —In patients with acute pulmonary embolism, transesophageal echocardiography (TEE) often reveals presumably thrombotic lesions within the central pulmonary arteries (CPAs). These CPA lesions, when found in patients with primary pulmonary hypertension, have been attributed to in situ thrombosis or atherosclerosis. We hypothesized that similar CPA lesions may also develop in patients with chronic obstructive pulmonary disease (COPD) in the absence of pulmonary embolism. Methods and Results —We examined by TEE 25 patients with COPD and 27 control patients with left heart disease. None of the patients had previous pulmonary embolism or ileofemoral and popliteal vein thrombosis. By use of TEE, CPA lesions were found in 12 COPD patients (48%) and 2 control patients (7.4%) ( P &lt;0.01). When CPA lesions were subdivided into types 1 (protruding and mobile) and 2 (wall-adherent), type 1 lesions proved to be uncommon, being found within the pulmonary trunk in 12% and 3.7% of COPD and control patients, respectively ( P =NS). Conversely, type 2 lesions, which were always localized in the right pulmonary artery, were frequent in COPD patients (36%) and rare in control patients (3.7%) ( P &lt;0.01). When available, helical CT and MR angiography confirmed TEE findings, supporting an atherosclerotic origin of type 2 lesions, which were different from typical thrombotic lesions. FEV 1 /FVC ratio, RV/TLC ratio, Pa o 2 , hematocrit value, and pulmonary artery systolic pressure were not significantly different in COPD patients with and without CPA lesions. At TEE, however, COPD patients with CPA lesions showed a larger size of the main and right pulmonary arteries. Conclusions —TEE often reveals CPA lesions in stable patients with COPD even in the absence of significant pulmonary hypertension and not in close relation with the severity of pulmonary dysfunction.
Psychiatric Emergencies: Intervention and Resolution
Authors: Norman R. Bernstein
Journal: JAMA (1984)

This is a handbook of psychiatric emergencies. It is written by two psychiatrists, a nurse, and a resident in psychiatry. The book undertakes to examine in a concise manner the major issues that are initially seen in a psychiatric emergency setting and to delineate techniques of diagnosis and management. The authors clearly describe the trends in emergency psychiatry caused by the increased number of people requiring crisis care and the shift in government support for emergency medicine. They point out that a different style is needed in urgent, emergency, and crisis work. They provide such helpful information as a "mini mental health examination" for evaluation of cognitive function, part of their awareness of constraints of the emergency situation. This book has a strong medical orientation and gives attention to the physical illnesses that may cause emotional symptoms and the varied chemical agents that may derange mental functioning. The authors point
Congress too prescriptive in saying how president's AIDS fund should be spent, report says
Authors: Bob Roehr
Journal: BMJ (2007)

The US president's international emergency plan for AIDS relief (PEPFAR), announced in President Bush's state of the union address in 2003, has made a good start to meeting its ambitious goals, a report by the independent Institute of Medicine said last week. 

But the report criticises the Congress's specification of how the money must be spent, with 55% to be spent on medical treatment and 20% on prevention, a third of which must be spent on abstinence-only programmes.

“Having the same budget allocation formula for 15 countries with very different kinds of epidemics is not useful,” said Jaime Sepulveda, chairman of the committee that conducted the evaluation and former director of the National Institutes of …
THE NEW IMMIGRATION AS IT AFFECTS ORTHOPEDIC SURGERY
Authors: WALLACE BLANCHARD
Journal: JAMA (1913)

A larger number of severe rachitis deformities of the legs have been rapidly corrected by bloodless osteoclasis in Chicago than in any half dozen other cities in the world. The records of the Chicago free orthopedic hospitals and dispensaries show that the new immigrant gives them eight times their normal ratio of rachitic deformities, four times their normal ratio of tuberculous deformities. Chicago is perhaps the only city in the world having winters of ice and snow that harbors twenty thousand new emigrants from tropical or semitropical countries every year, and very bad rachitic deformities are almost peculiar to the children of recent immigrants from hot to cold climates. The people from Northern Europe huddle closely. Their children double our tuberculous joint deformities. The german and Russian Jew girls are especially prone to scoliosis. Dr. Peter Roberts, in his book<sup>1</sup>presents a map of the United States, with a line drawn from Atlantic City to Cairo, Ill., and thence to the northwest
Understanding Neurological Disease Mechanisms in the Era of Epigenetics
Authors: Irfan A. Qureshi, Mark F. Mehler
Journal: JAMA Neurology (2013)

The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues.
Contribution of dihydrotestosterone to male sexual behaviour
Authors: C. S Mantzoros, E. I Georgiadis, D. Trichopoulos
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To document the relative importance of endogenous sex steroids in modulating the frequency of orgasms, the dominant aspect of sexual behaviour in healthy eugonadal men. <b>Design</b>: Measurement of adrenal and testicular sex steroids in a sample of army recruits and study of their relation to frequency of orgasms ascertained by questionnaire after potential confounding variables were controlled for. <b>Setting</b>: Military campus and military hospital laboratories in Athens, Greece. <b>Subjects</b>: 92 consecutively enrolled healthy male recruits aged 18-22 years. <b>Main outcome measures</b>: Weekly number of orgasms. Serum concentrations of testosterone, dehydroepiandrosterone sulphate, dihydrotestosterone, oestradiol, oestrone, δ-4-androstenedione, and sex hormone binding globulin. <b>Results</b>: Serum dihydrotestosterone concentration was the only independent hormonal predictor of the frequency of orgasms; an increase in concentration of 1.36 nmol/l (about 2 SD) corresponded to an average increase of one orgasm a week. <b>Conclusions</b>: Differences in concentrations of circulating dihydrotestosterone within the normal range may represent a major predictor of sexual activity in healthy young men. <h3>Key messages</h3> Key messages The hormone that determines sexual behavior has not yet been conclusively identified in healthy adults This study shows that dihydrotestosterone is the dominant hormonal determinant of the frequency of orgasms in young healthy adults The frequency of orgasms depends not only on psychosocial factors but on variation of dihydrotestosterone concentrations within the normal range
Junctional Tachycardia
Authors: KENNETH M. ROSEN
Journal: Circulation (1973)

IN THE ABSENCE of functioning anomalous connection between atria and ventricles, the A-V junction serves as the only link between these structures, allowing the atrial impulse to be transmitted to the ventricles.The A-V junction may be defined as consisting of the atrial approaches to the A-V node, the A-V node itself, and the penetrating portion of the His bundle.Total transection of the A-V junction at any point should produce A-V block, and stimulation in the presence of a normal His-Purkinje system should produce a narrow QRS.The electrophysiologic function of the A-V junction is primarily that of conduction.However, in addition, the A-V junction possesses intrinsic automaticity, allowing it to serve as a subsidiary pacemaker in the event of failure of proximal impulse formation or propagation.Under pathologic conditions, the A-V junction can serve as an ectopic pacemaker, or as a site of reentry. Electrophysiologic ConsiderationsExperimental studies demonstrating automaticity in the A-V junction were extensively reviewed by Scherf and Cohen.1 Earlier workers produced A-V junctional escape rhythms after depressing sinus node function by various surgical, chemical, mechanical, and thermal maneuvers.In addition, experimental A-V junctional rhythms were pro- duced by increasing sympathetic tone or by warming specific areas in the A-V junction.The site of origin in the A-V junction was determined by noting the timing of atrial and ventricular contrac- tion, and also by noting the initial sites of negativity with direct recording.Zahn suggested classification into upper, middle, and lower A-V nodal rhythms.2In upper nodal rhythms, atrial contraction preceded
REDUCED DEFORMATION AND HIGHER CALCIFICATION OF THE AORTIC ANNULUS PREDICTS POST–PROCEDURAL AORTIC INSUFFICIENCY IN PATIENTS UNDERGOING TAVR: A MULTI–MODALITY IMAGING STUDY
Authors: Ahmad Masri, Paul Schoenhagen, Samir Kapadia, Lars Svensson, E. Murat Tuzcu, Milind Desai
Journal: Journal of the American College of Cardiology (2013)
Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats
Authors: Laura G. Sanchez-Lozada, Edilia Tapia, Jose Santamaria, Carmen Avila-Casado, Virgilia Soto, Tomas Nepomuceno, Bernardo Rodriguez-Iturbe, Richard J. Johnson, Jaime Herrera-Acosta
Journal: Kidney International (2004)
Experimental Hepatitis Induced by Ethanol After Immunization with Acetaldehyde Adducts
Authors: Hirokazu Yokoyama, Hiromasa Ishii, Shigeyuki Nagata, Shinzo Kato, Kiyotaka Kamegaya, Masaharu Tsuchiya
Journal: Hepatology (1993)

We produced hepatitis in guinea pigs by immunization with acetaldehyde adducts and ethanol treatment. Human hemoglobin-acetaldehyde adducts were prepared without any reducing agents and affinity purified with polyclonal antibodies against acetaldehyde adducts. Female guinea pigs were immunized with the adducts and were simultaneously given ethanol for 40 days. These treatments induced hepatic necrosis with infiltration of mononuclear cells in the hepatic lobules. The formation of the lymphoid follicle was also observed in severe cases. These changes were accompanied by the elevation of serum AST and lactic dehydrogenase activities and titers of circulating antibodies against acetaldehyde adducts. By contrast, the combination of ethanol and immunization with unmodified hemoglobin produced only fatty change of the liver, and animals immunized with the adducts alone had minimal inflammatory changes of the liver. Peripheral blood lymphocytes obtained from the animals with hepatitis were shown to be stimulated by acetaldehyde adducts to a significantly greater degree than those from control animals who received nothing, ethanol alone or ethanol and unmodified hemoglobin. These results suggest that the immune response to acetaldehyde adducts may be involved, at least partly, in the pathogenesis of inflammation observed in alcoholic liver disease.