tbuckley/cabot-search huggingface dataset:
New school in liver development: Lessons from zebrafish
Authors: Jaime Chu, Kirsten C. Sadler
Journal: Hepatology (2009)

Abstract There is significant overlap in the genes and pathways that control liver development and those that regulate liver regeneration, hepatic progenitor cell expansion, response to injury, and cancer. Additionally, defects in liver development may underlie some congenital and perinatal liver diseases. Thus, studying hepatogenesis is important for understanding not only how the liver forms, but also how it functions. Elegant work in mice has uncovered a host of transcription factors and signaling molecules that govern the early steps of hepatic specification; however, the inherent difficulty of studying embryogenesis in utero has driven developmental biologists to seek new systems. The rapidly developing vertebrate zebrafish is a favorite model for embryology. The power of forward genetic screens combined with live real-time imaging of development in transparent zebrafish embryos has highlighted conserved processes essential for hepatogenesis and has uncovered some exciting new players. This review presents the advantages of zebrafish for studying liver development, underscoring how studies in zebrafish and mice complement each other. In addition to their value for studying development, zebrafish models of hepatic and biliary diseases are expanding, and using these small, inexpensive embryos for drug screening has become de rigueur . Zebrafish provide a shared platform for developmental biology and translational research, offering innovative methods for studying liver development and disease. The story of hepatogenesis has something for everyone. It involves transcriptional regulation, cell-cell interaction, signaling pathways, control of cell proliferation and apoptosis, plus morphogenic processes that sculpt vasculature, parenchymal cells, and mesenchyme to form the multifaceted liver. Decades of research on liver development in mice and other vertebrates offer valuable lessons in how the multipotent endoderm is programmed to form a functional liver. Of equal importance are insights that have illuminated the mechanisms by which hepatic progenitors are activated in a damaged liver, how the adult liver regenerates, and, possibly, the basis for engineering liver cells in vitro for cell transplantation to sustain patients with liver failure. Moreover, processes that are key to liver development are often co-opted during pathogenesis. Therefore, reviewing hepatogenesis is informative for both basic and translational researchers. In this review, we bring to light the many advantages offered by the tropical freshwater vertebrate zebrafish ( Danio rerio ) in studying hepatogenesis. By comparing zebrafish and mice, we highlight how work in each system complements the other and emphasize novel paradigms that have been uncovered using zebrafish. Finally, we highlight exciting efforts using zebrafish to model hepatobiliary diseases. (Hepatology 2009.)
Rapid Electrical Stimulation of Contraction Reduces the Density of β-Adrenergic Receptors and Responsiveness of Cultured Neonatal Rat Cardiomyocytes
Authors: Hidetoshi Yonemochi, Seikoh Yasunaga, Yasushi Teshima, Naohiko Takahashi, Mikiko Nakagawa, Morio Ito, Tetsunori Saikawa
Journal: Circulation (2000)

Although tachycardia is commonly present in patients with congestive heart failure, its role in the development of congestive heart failure remains unclear. We studied the effect of rapid electrical stimulation of contraction on beta-adrenergic receptor (beta-AR) signal pathway in cultured cardiomyocytes of neonatal rats.Contraction of cardiomyocytes was induced by electrical stimulation at 50 V with twice the threshold pulse width. beta-ARs were identified by [(3)H]CGP-12177 and [(3)H]dihydroalprenolol. Electrical stimulation reduced cell-surface but not total beta-AR density; the effect was dependent on pacing frequency (a reduction of 11%, 28%, and 18% in cells paced at 2.5, 3. 0, and 3.3 Hz, respectively). This reduction was apparent at 3 hours, in contrast to reduced beta-AR density after exposure to isoproterenol (ISP) for 1 hour. The fraction and inhibition constant of beta-AR binding agonist with high affinity were not affected by rapid electrical stimulation. In cardiomyocytes paced at 3.0 Hz for 24 hours, the response to ISP decreased compared with unpaced cells, 142% versus 204% of baseline with 1 micromol/L ISP, whereas the responses to forskolin or acetylcholine were not different. Treatment of cardiomyocytes with 2,3-butanedione monoxime (10 mmol/L) or taxol (10 micromol/L) inhibited the rapid pacing-induced reduction in beta-AR density.Our results suggest that contractile activity is involved in regulation of cardiac function by modulating the beta-AR system independently of hemodynamic and neurohormonal factors. This may help to elucidate the role of mechanical stress in the development of heart failure.
The Quality of Children's Health Care Matters — Time to Pay Attention
Authors: James M. Perrin, Charles J. Homer
Journal: New England Journal of Medicine (2007)

High-quality health care matters for all children — and is critically important for some. In many ways, health care for children serves the same function as health care for adults. For example, the incidence of chronic illness in children is increasing, resulting in a substantial illness burden with a substantial cost.1 How well chronic conditions are managed profoundly influences both short-term and long-term outcomes, not only for common diseases such as asthma but also for rarer conditions such as cancer, cystic fibrosis, and sickle cell disease.2 Many aspects of children's health care have no parallel in adult health services.3 The . . .
Signal averaged ECG in patients with LBBB pattern ventricular tachycardia: Correlation with radionuclide fourier phase abnormalities
Authors: Dominique Le Guludec, Robert Frank, Maya Namade, Jean-Marc Davy, Michel Slama, Héric Valette, Antoine Leenhardt, Guy Fontaine, Gilbert Motté, André Syrota
Journal: Journal of the American College of Cardiology (1991)
Doctors Under Hitler
Authors: Eugene Y. Boisaubin
Journal: JAMA (1990)

As living memory of the Third Reich slowly dies, interest in permanently chronicling this unprecedented period becomes an imperative. Fortunately, a flurry of recent academic studies, specifically focusing on the health professions, has analyzed elements of the most catastrophic corruption of the medical profession in modern Western history.<sup>1,2</sup> Michael Kater, a well-credentialed historian of the Nazi period, has pains-takingly and systematically analyzed the circumstances, people, and forces that changed and motivated German medicine from 1933 to 1945. Previously, hundreds of years of anti-Semitism and xenophobia had created a receptive soil in which racist social and political policy was later able to supplant a highly developed scientific tradition.<i>Rassenkunde</i>, or race hygiene (also referred to as "eugenics"), was a hallmark of the National Socialist doctrine. Nazi leaders adroitly cultivated these theories, originally created by physician-scientists, in the universities and schools of medicine. They also exploited physicians' innate elitism, idealism (the
INTERESTING ASPECTS OF A CASE OF CONGENITALLY ABSENT GALLBLADDER
Authors: Meyer Golob
Journal: JAMA (1927)

This is a case of a congenitally absent gallbladder. It is worthy of report, first, because of its comparative rarity; secondly, because it indicates the closeness of the diagnostic relationship between biliary drainage and cholecystography, both of which were used in the course of the search for the source of the symptoms; and, thirdly, because it illustrates an interesting aspect of the mental process involved in making a diagnosis. <h3>REPORT OF CASE</h3> M. B., a married woman, aged 59, a multipara, had typhoid when she was 23, and, as its sequel, suffered a pain extending throughout the lower right extremity for many years. At 30 she had a "nervous breakdown," which continued for several months. The menopause came at 50, without vasomotor disturbance. At 53 she had influenza for several weeks. The illness in this case had a duration of four years. The chief complaints were an explosive
Symptoms of low blood pressure.
Authors: L O Simpson
Journal: BMJ (1990)

Overall effects of lowering cholesterol on coronary heart disease.(Results of six trials, n= 12457 in treated groups, n= 12 390 in control groups)No of events Sum of Overall odds ratio Type of coronary event (treated/control) observed-expected events* (95% confidence interval) p ValueNon-fatal 368/495 -63 5 0 73 (0-64 to 0 84) 0 00 Fatal 169/197 -14-0 0 85 (069 to 1-05) 0-06 All 523/670 -73 5 0 77 (0-68 to 0 86) 0 00 *The sum of observed-expected events in the combined trials, as used in the meta-analysis, is half of the actual difference in events (treated -control) when the treated and control groups are of equal size.
Autophagy activation by rapamycin eliminates mouse Mallory-Denk bodies and blocks their proteasome inhibitor-mediated formation
Authors: Masaru Harada, Shinichiro Hanada, Diana M. Toivola, Nafisa Ghori, Bishr M. Omary
Journal: Hepatology (2008)

The proteasomal and lysosomal/autophagy pathways in the liver and other tissues are involved in several biological processes including the degradation of misfolded proteins. Exposure of hepatocyte cell lines to proteasome inhibitors (PIs) results in the formation of inclusions that resemble Mallory-Denk bodies (MDBs). Keratins are essential for MDB formation and keratin 8 (K8)-overexpressing transgenic mice are predisposed to MDB formation. We tested the hypothesis that PIs induce MDBs in vivo and that autophagy participates in MDB turnover. The effect of the PI bortezomib (which is used to treat some malignancies) on MDB formation was tested in K8-overexpressing mice and in cultured cells. Inclusion formation was examined using immune and conventional electron microscopy (EM). Bortezomib induced MDB-like inclusions composed of keratins, ubiquitin, and p62 in cultured cells. Short-term exposure to bortezomib induced similar inclusions in K8-overexpressing but not in nontransgenic mice, without causing liver injury. In bortezomib-treated mice, autophagy was activated in hepatocytes as determined by EM and biochemical analysis. Further activation of autophagy by rapamycin (Rap) decreased the number of inclusions in bortezomib-treated K8 transgenic mice significantly. Rap also led to resorption of spontaneously formed MDBs in aging K8-overexpressing mice. Immune EM demonstrated K8-positive and ubiquitin-positive structures in autophagic vacuoles in the mouse liver. Conclusion: PIs alone are sufficient to induce MDBs in susceptible animals, while Rap-mediated activation of autophagy prevents MDB formation and causes MDB resorption. These findings suggest that some patients treated with PIs may become predisposed to MDB formation. Autophagy provides a potential cellular mechanism for the resorption of cytoplasmic inclusions.
Aortic Valvuloplasty under Direct Vision
Authors: J. Gordon Scannell, Robert S. Shaw, John F. Burke, W. Gerald Austen, Alejandro H. Villegas, Richard R. Kelley
Journal: New England Journal of Medicine (1960)

THERE have been many published reports dealing with the surgical management of aortic stenosis since Tuffier, in 1913, first attempted to correct this defect by invagination of the aortic wall and dilatation of the aortic valve. A number of "closed" and "open" technics have been described. In general they have been characterized by high operative mortality, inconsistent relief of stenosis and the production of significant degrees of aortic regurgitation. The purpose of this report is to present our opinions, which are the product of a series of perfusion studies in the autopsy room, a limited and unsatisfactory experience with "closed" . . .
Studies Examine Fetal Surgery Trade-offs, Drug Interactions, and Uterine Rupture
Authors: Bridget M. Kuehn
Journal: JAMA (2012)

AS IMAGING TECHNOLOGIES MAKE it easier to identify congenital abnormalities that might be treated through fetal surgery, clinicians and parents face difficult choices about whether to pursue such innovative treatment or to plan for corrective procedures after birth. As the Agency for Healthcare Research and Quality noted earlier this year, so far there are limited data to guide such choices (http://tinyurl.com/6o7zoa3). But a study presented at the Society for Maternal Fetal Medicine’s annual meeting in Dallas in February may help fill this gap, at least for parents and clinicians considering when to perform surgery for spina bifida diagnosed in utero. Researchers concluded that carrying out corrective surgery in utero for myelomeningocele, a bulge of spinal cord that protrudes through the spine, was costeffective compared with delaying surgery until after birth, but that risks to the mother and any subsequent children require careful consideration. Otherstudiespresentedat themeeting included one that identified potential warning signs that may precede uterine rupture in patients attempting a vaginal birthaftercesareandelivery,andanother thatdocumentedpotentialmedicationinteractionsthatmayaffect themetabolism of 17-hydroxyprogesterone caproate (17-OHPC), a drug approved by the US FoodandDrugAdministration(FDA)to help prevent preterm delivery.
Chronic abdominal pain in children
Authors: M Y Berger, M J Gieteling, M A Benninga
Journal: BMJ (2007)

Chronic abdominal pain is a common disorder in children and adolescents worldwide. It affects the child's wellbeing, and the costs from missed school days and use of healthcare resources are high. 

Children with chronic abdominal pain represent a heterogeneous population comprising both organic and functional gastrointestinal disorders. Functional disorders are those that cannot be explained by structural or biochemical abnormalities. Differences in prevalence of organic disease are reported depending on the setting, ranging from 5% in the general population to 40% in a paediatric gastroenterologist practice.1 General practitioners feel confident in labelling chronic abdominal pain as an easy to manage functional disorder. After minimal further testing, these children and their parents can be reassured by explaining that the symptoms are common and rarely associated with disease. However, when diagnostic uncertainty increases, pain does not resolve over time, or parents are hard to reassure, extensive testing and referral easily set in. As a consequence paediatricians perceive chronic abdominal pain as a time consuming and therapy resistant disorder.

#### SUMMARY POINTS

#### Sources and selection criteria

We used the Cochrane library to identify relevant systematic reviews that evaluated the effectiveness of pharmaceutical, psychological, and complementary interventions for chronic abdominal pain in children.

Medline searches were used to find relevant systematic reviews on diagnosis and treatment of abdominal pain in children using the keywords “abdominal …
Anti-MJ/NXP-2 antibodies are the most common specifcity in a cohort of adult caucasian patients with dermatomyositis
Authors: Angela Ceribelli, Micaela Fredi, Mara Taraborelli, Ilaria Cavazzana, Franco Franceschini, Angela Tincani, Steven J Ross, Brad A Pauley, Edward K L Chan, Minoru Satoh
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background/objective</h3> Specific autoantibodies in patients with polymyositis/dermatomyositis (PM/DM) are associated with unique subsets, and they are useful in monitoring clinical course and predicting outcome. Anti-MJ antibodies, which recognise the nuclear protein NXP-2 in PML (promyelocytic leukemia) nuclear bodies, are a new specificity reported in 23–25% of juvenile DM, usually associated with severe muscle atrophy, functional impairment, and calcinosis. The aim of our study is to analyse the prevalence and clinical significance of anti-MJ antibodies in a cohort of adult Caucasian PM/DM patients. <h3>Methods</h3> Autoantibodies in sera from 58 consecutive adult PM/DM patients (74% female, mean age 43+/−17, mean follow-up 55 months) were analysed by immunoprecipitation of 35S-labeled K562 cell extracts, ELISA (anti-MJ, Ro52, La, Jo-1), Western Blot and Indirect Immunofluorescence (IIF). Clinical association of anti-MJ was analysed using information from charts and database. <h3>Results</h3> Anti-MJ antibodies are the most prevalent specificity (10/58; 17%) in our PM/DM cohort, followed by anti-Jo-1 (10%), -p155/140 (5%), -SRP (5%), -EJ (4%) and anti-Mi-2, -SMN complex, -OJ with one case each. Anti-MJ was found in 30% of DM and 8% of PM (p: 0.02). Among 10 cases of anti-MJ, 8 were DM and 2 were PM. When clinical features of 10 cases of anti-MJ (+) versus 48 cases anti-MJ (-) were compared, DM is more common (p: 0.03) and no overlap syndrome patients were found in anti-MJ group (0% vs 13%). Age of onset (25.5 vs 46.1 years) and age at initial visit (37.6 vs 54.6 years) were younger in anti-MJ group (p: 0.002), and 2 anti-MJ (+) were pediatric onset DM. In anti-MJ (+) patients, heliotrope rash (p:0.01) and calcinosis (p:0.057) were common, however, none of them had heart involvement (0% vs 27%, p:0.03), interstitial lung disease (0% vs 33%, p:0.048), or cancer (0% vs 8%). Myopathy in anti-MJ (+) patients showed a good response to steroid therapy. Only 6/10 anti-MJ (+) showed PML body nuclear dots staining in IIF, suggesting that IIF cannot be used for screening of anti-MJ antibodies. <h3>Conclusion</h3> Anti-MJ antibodies are detected also in adult PM/DM, and they are the most frequent specificity in our cohort, found in 17% of PM/DM (30% in DM and 8% in PM). Anti-MJ (+) patients showed DM of young onset with a mild myopathy, severe calcinosis and without internal organ involvement. Anti-MJ will be a useful new addition of myositis-associated autoantibodies to help clinical monitoring of patients with adult PM/DM.
INTUSSUSCEPTION CONTAINING A SARCOMA OF THE INTESTINAL WALL: ENTERECTOMY: RECOVERY
Authors: C. A. S. Ridout, J. F. Palser
Journal: BMJ (1909)

INT1T8SU8CEPTION CONTAINING A SARCOMA. r M .O839 k r .3,gQg.'I TINuIZ Bamsw" -83,g abdominal pain in her right iliac region, left shoulder and arm.This pain diminished after a couple of hours but later again increased in severity.Pain remained agoaizing during the night and extended from the right iliac fossa all over the abdomen.No vomiting occurred after the onset of severe pain Sihe was admitted to hospital at 8 p.m. on November 24th, 1905,
Audit report criticises India's slow progress on AIDS
Authors: Ganapati Mudur
Journal: BMJ (2004)

An Indian government audit has said that the national AIDS control programme has achieved only limited success because of slow implementation, unachieved targets, and ineffective public education.

In a report presented to the Indian parliament last week, India's comptroller and auditor general said that various activities under the programme could not be conducted efficiently for lack of infrastructure, drugs, equipment, and human resources.

The report, which examined the programme's activities between 1999 and 2003, has listed among the deficiencies misconceptions about HIV transmission, a shortfall in the training of doctors, nurses, and technicians, and the failure of marketing of condoms. It said targeted intervention, viewed as the most effective strategy to …
Idiopathic pulmonary haemosiderosis: a form of microscopic polyarteritis?
Authors: B Leaker, G Cambridge, R M du Bois, G H Neild
Journal: Thorax (1992)

Idiopathic pulmonary haemosiderosis remains a diagnosis of exclusion in patients who present with pulmonary alveolar haemorrhage. Systemic vasculitis developed in a patient with an eight year history of idiopathic pulmonary haemosiderosis. The diagnosis was confirmed by a rising titre of antineutrophil cytoplasmic antibodies directed against myeloperoxidase. Treatment with immunosuppressive agents resulted in complete resolution of symptoms and suppression of the antibodies. Measurement of antineutrophil cytoplasmic antibodies is recommended for all patients with pulmonary alveolar haemorrhage syndromes.
THE TREATMENT OF IMMATURE CATARACT AND WHEN TO OPERATE FOR CATARACT.Remarks made in a Conference During the Special Week on Cataract.
Authors: Geo. E. de Schweinitz
Journal: JAMA (1894)

Dr. de Schweinitz, referring to the medicinal treatment of cataract, stated that no drugs were known which could dissipate lenticular opacities. Occasionally there was spontaneous disappearance of cataract, for example, in diabetic patients; and even, if certain reports are to be credited, for example those by Nicati, of true senile cataract; but such disappearance could not be ascribed to the influence of medicine. In like manner, electricity, which from time to time has been recommended, is of doubtful value; in fact, there is no evidence to show that electrical currents have ever had the slightest influence in checking the growth of lenticular opacities. These statements, however, do not conflict with the propriety of treating the subjects of lenticular opacities; 1, by careful testing of the refractive error and prescribing the glass which gives the highest visual acuity; and 2, by exhibiting alteratives, particularly the iodids of soda and potash, sedatives,
Sociobiology: The New Synthesis
Authors: Marjorie C. Meehan
Journal: JAMA (1975)

"Sociobiology is... the systematic study of the biological basis of all social behavior," explains the author, professor of zoology at Harvard. Although a new discipline, sociobiology is obviously an important, interesting subject, covering a wide field. And this remarkable book covers the field very well. How do members of a species relate to each other, how do they cooperate, how do they compete? Why have so many different patterns of social behavior developed? Are the behaviors genetically determined, learned, or the result of chance? When and why do altruism, aggression, male dominance, caste systems, parasitism, slavery, self-sacrifice occur in the animal kingdom? In this book is gathered a wealth of material to answer many of these questions. Extensive chapters are devoted to social evolution, population biology, group selection, communication, territoriality, dominance, parental care. Then the various types of organisms— microorganisms, insects, cold-blooded vertebrates, birds, and several kinds of mammals—are discussed
A surfeit of screening?
Authors: P. G Griffiths
Journal: BMJ (1997)

It is now Wednesday. So far this week I have attended three planned eye clinics and a eye casualty session. I do not normally work in eye casualty, but there have been dark rumours about the pressure of work, and our ophthalmic senior house officers seem to be wilting under the strain. It is clearly time to investigate the problem.

The outpatient sessions have included one adult clinic in a teaching hospital, one outreach clinic in a rural area, and a children's clinic back at base. Relatively few patients have symptoms. Most have been referred following screening programmes or opportunistic case finding (a euphemism for limited screening which evades the normal considerations of sensitivity, specificity, ethics, and cost).

In my adult clinic the commonest indication for referral is raised intraocular pressure indicating possible glaucoma. But pressure alone is a poor way of screening for glaucoma and a recent meta-analysis of medical treatment of glaucoma failed to show any beneficial effect of screening in terms of preserving vision. …