tbuckley/cabot-search huggingface dataset:
Concurrent expression of erythroid and renal aquaporin CHIP and appearance of water channel activity in perinatal rats.
Authors: B L Smith, R Baumgarten, S Nielsen, D Raben, M L Zeidel, P Agre
Journal: Journal of Clinical Investigation (1993)

Major phenotypic changes occur in red cell membranes during the perinatal period, but the underlying molecular explanations remain poorly defined. Aquaporin CHIP, the major erythroid and renal water channel, was studied in perinatal rats using affinity-purified anti-CHIP IgG for immunoblotting, flow cytometry, and immunofluorescence microscopy. CHIP was not detected in prenatal red cells but was first identified in circulating red cells on the third postnatal day. Most circulating red cells were positive for CHIP by the seventh postnatal day, and this proportion rose to nearly 100% by the 14th day. The ontogeny of red cell CHIP correlated directly with acquisition of osmotic water permeability and inversely with Arrhenius activation energy. Only minor alterations in the composition of red cell membrane lipids occurred at this time. Immunohistochemical analysis of perinatal kidneys demonstrated a major induction of CHIP in renal proximal tubules and descending thin limbs at birth, coincident with the development of renal concentration mechanisms. Therefore, water channels are unnecessary for oxygen delivery or survival in the prenatal circulation, however CHIP may confer red cells with the ability to rehydrate rapidly after traversing the renal medulla, which becomes hypertonic after birth.
Effects of nifedipine on left ventricular diastolic function in patients with asymptomatic or minimally symptomatic hypertrophic cardiomyopathy.
Authors: T Yamakado, H Okano, S Higashiyama, M Hamada, T Nakano, H Takezawa
Journal: Circulation (1990)

We investigated the effects of nifedipine on left ventricular diastolic function in 17 asymptomatic or minimally symptomatic patients with hypertrophic cardiomyopathy by simultaneously measuring left ventricular pressure and volume with a catheter-tipped manometer and biplane cineangiography. Studies were performed before and 20 minutes after sublingual administration of nifedipine (20 mg). Heart rates were held constant (79 +/- 12 beats/min, mean +/- SD) by right atrial pacing. Left ventricular volumes and instantaneous rates of left ventricular volume were derived from frame-by-frame (20-msec) analyses of left ventricular biplane angiograms. Left ventricular peak systolic pressure (from 122 +/- 21 to 108 +/- 13 mm Hg, p less than 0.01 vs. control) and mean aortic pressure (from 96 +/- 15 to 87 +/- 11 mm Hg, p less than 0.01) decreased significantly with nifedipine. With afterload reduction, left ventricular ejection fraction (from 0.69 +/- 0.12 to 0.74 +/- 0.08, p less than 0.01) and cardiac output (from 6.4 +/- 2.0 to 7.2 +/- 2.2 l/mm, p less than 0.05) increased significantly. However, there was a slight but significant increase in left ventricular end-diastolic pressure (from 15 +/- 8 to 18 +/- 8 mm Hg, p less than 0.05). Nifedipine did not improve left ventricular relaxation as assessed by the time constants of isovolumic pressure decay (t1/2, from 39.8 +/- 6.6 to 39.4 +/- 7.7 msec, NS; t1/e, from 53.8 +/- 9.0 to 54.4 +/- 10.7 msec, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Everybody's free (to wear sunscreen): the power of pop
Authors: S.A. Holme, J. Evans, C. Roberts, D.L. Roberts
Journal: British Journal of Dermatology (2001)

Sir, It is widely accepted that teenagers are a difficult group to influence with health education messages,1 and as discussed by Melia et al.2 there are few studies of this age group in the U.K. with respect to primary prevention initiatives for skin cancer. Two recent studies in teenagers used educational videos and literature, and showed that education resulted in increased awareness, a positive attitude to sun protection/avoidance and increased sunscreen use when evaluated at 4 months after intervention.3,4 The pop single Everybody's free (to wear sunscreen) by Baz Lurman was in the U.K. charts for 4 weeks in June 1999, and at number one for 1 week. The recording was a parody of a speech to high‐school students, offering advice on lifestyle. The opening and closing statements strongly extolled the use of sunscreen, an example being: ‘If I could offer you only one tip for the future, sunscreen would be it. The long‐term benefits of sunscreen have been proved by scientists, whereas the rest of my advice has no basis more reliable than my own meandering experience’. To assess the influence of this novel form of health education on teenagers, 381 children aged 11–14 years (185 boys, 196 girls; mean age 13·1 years) were asked to complete a questionnaire during school sessions, 3 months after the song reached number 1. The response rate was 100%. A greater proportion of girls (93·3%) recalled hearing the recording in comparison with boys (68·1%) (95% confidence interval, CI 18·1–33·1; P < 0·001). The differences in regular sunscreen use between the groups who recalled hearing the song and those who did not were not significant. Overall, girls (72%) were more likely to be regular users of sunscreen than boys (43%) (95% CI 3·7–24·8; P < 0·01). As a result of hearing the recording, 42·4% of girls and 38·1% of boys stated that their attitude to sun protection had changed, and that they would be more likely to use sunscreen or use it more frequently as a result of listening to the track (not statistically significant).
Salience Network–Based Classification and Prediction of Symptom Severity in Children With Autism
Authors: Lucina Q. Uddin, Kaustubh Supekar, Charles J. Lynch, Amirah Khouzam, Jennifer Phillips, Carl Feinstein, Srikanth Ryali, Vinod Menon
Journal: JAMA Psychiatry (2013)

Autism spectrum disorder (ASD) affects 1 in 88 children and is characterized by a complex phenotype, including social, communicative, and sensorimotor deficits. Autism spectrum disorder has been linked with atypical connectivity across multiple brain systems, yet the nature of these differences in young children with the disorder is not well understood.To examine connectivity of large-scale brain networks and determine whether specific networks can distinguish children with ASD from typically developing (TD) children and predict symptom severity in children with ASD.Case-control study performed at Stanford University School of Medicine of 20 children 7 to 12 years old with ASD and 20 age-, sex-, and IQ-matched TD children.Between-group differences in intrinsic functional connectivity of large-scale brain networks, performance of a classifier built to discriminate children with ASD from TD children based on specific brain networks, and correlations between brain networks and core symptoms of ASD.We observed stronger functional connectivity within several large-scale brain networks in children with ASD compared with TD children. This hyperconnectivity in ASD encompassed salience, default mode, frontotemporal, motor, and visual networks. This hyperconnectivity result was replicated in an independent cohort obtained from publicly available databases. Using maps of each individual's salience network, children with ASD could be discriminated from TD children with a classification accuracy of 78%, with 75% sensitivity and 80% specificity. The salience network showed the highest classification accuracy among all networks examined, and the blood oxygen-level dependent signal in this network predicted restricted and repetitive behavior scores. The classifier discriminated ASD from TD in the independent sample with 83% accuracy, 67% sensitivity, and 100% specificity.Salience network hyperconnectivity may be a distinguishing feature in children with ASD. Quantification of brain network connectivity is a step toward developing biomarkers for objectively identifying children with ASD.
Precise mapping of the Goodpasture epitope(s) using phage display, site-directed mutagenesis, and surface plasmon resonance
Authors: Roberto Gozalbo-Rovira, Jesús Rodríguez-Díaz, Juan Saus, Javier Cervera
Journal: Kidney International (2012)

Goodpasture disease is an autoimmune disorder mediated by circulating autoantibodies against the noncollagenous-1 (NC1) domain of the α3 chain of type IV collagen (α3(IV)NC1). The structure of Goodpasture epitope(s) has been previously mapped into two main binding regions (E(A) and E(B)) of the α3(IV)NC1 domain using a residue mutation approach on the highly related α1(IV)NC1 domain. Here we combined phage display and surface plasmon resonance technology to more precisely localize the pathogenic binding sites. Peptides mimicking the Goodpasture epitope(s) were used to identify residues involved in autoantibody binding and found involvement of eight residues previously unrecognized within and outside of the E(A) or E(B) regions. Residue involvement in pathogenic reactivity was confirmed by site-directed mutagenesis on a more divergent α2(IV)NC1 molecule. From a mutant (M1) of the α2(IV)NC1 molecule, harboring residues previously identified as belonging to the Goodpasture epitope, additional chimeras were generated on the bases of phage display findings. All these mutants were shown to display higher reactivity with circulating Goodpasture autoantibodies than the M1 mutant. Thus, our results more precisely define Goodpasture epitope determinants and open new avenues to delineate comprehensive autoantibody-blocking agents for therapeutics.
Abstract C52: Gene silencing of c-met leads to brain metastasis inhibitory effects
Authors: Se Jeong Lee, Hye Won Lee, Mi Young Song, Kee Hang Lee, Young-Eun Lee, Kyeung Min Joo
Journal: Cancer Research (2013)

Abstract An unfortunate consequence of improvements in the treatments of advanced primary cancers is the concurrent increase of metastatic brain tumors. Despite of unfavorable clinical prognosis, radiation therapy is still the only viable treatment option for brain metastases. Expression of c-Met induces cell migration and invasion in many cancers, which are indispensable steps for metastasis. Accordingly, we examined the effects of gene silencing of c-Met on brain metastasis to evaluate the possibility of c-Met as a potential target. MDA-MB-435 cells were transfected with c-Met targeting short hairpin RNAs (shRNAs). Effects of c-Met shRNAs on the expression of epithelial mesenchymal transition (EMT) related proteins, in vitro migration, and in vivo brain metastasis were examined. Expression of mesenchymal markers and in vitro migration of MDA-MB-435 cells were significantly inhibited by introduction of c-Met shRNAs. When c-Met-silenced MDA-MB-435 cells were stereotactically implanted into the brains of immune-compromised mice or injected into the right internal carotid arteries, c-Met-silenced MDA-MB-435 cells produced significantly smaller tumor masses or survival time was significantly prolonged, respectively, compared with MDA-MB-435 cells transfected with control shRNA. The data reveal the novel function of c-Met in the process of brain metastasis and its potential as a preventive and/or therapeutic target in this disease. Citation Format: Se Jeong Lee, Hye Won Lee, Mi Young Song, Kee Hang Lee, Young-Eun Lee, Kyeung Min Joo. Gene silencing of c-met leads to brain metastasis inhibitory effects. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C52.
Gastric acid suppression and risk of oesophageal and gastric adenocarcinoma: a nested case control study in the UK
Authors: L A G. Rodriguez, J Lagergren, M Lindblad
Journal: Gut (2006)

Gastric acid suppressing drugs (that is, histamine(2) receptor antagonists and proton pump inhibitors) could affect the risk of oesophageal or gastric adenocarcinoma but few studies are available.To study the association between long term treatment with acid suppressing drugs and the risk of oesophageal or gastric adenocarcinoma.Persons registered in the general practitioners research database in the UK and aged 40-84 years during the period 1994-2001.Population based nested case control study. Multivariable unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CI).In 4 340 207 person years of follow up, 287 patients with oesophageal adenocarcinoma, 195 with gastric cardia adenocarcinoma, and 327 with gastric non-cardia adenocarcinoma were identified, and 10 000 control persons were randomly sampled. "Oesophageal" indication for long term acid suppression (that is, reflux symptoms, oesophagitis, Barrett's oesophagus, or hiatal hernia) rendered a fivefold increased risk of oesophageal adenocarcinoma (odds ratio (OR) 5.42 (95% confidence interval (CI) 3.13-9.39)) while no association was observed among users with a group of other indications, including peptic ulcer and "gastroduodenal symptoms" (that is, gastritis, dyspepsia, indigestion, and epigastric pain) (OR 1.74 (95% CI 0.90-3.34)). "Peptic ulcer" indication (that is, gastric ulcer, duodenal ulcer, or unspecified peptic ulcer) was associated with a greater than fourfold increased risk of gastric non-cardia adenocarcinoma among long term users (OR 4.66 (95% CI 2.42-8.97)) but no such association was found in those treated for a group of other indications (that is, "oesophageal" or "gastroduodenal symptoms") (OR 1.18 (95% CI 0.60-2.32)).Long term pharmacological gastric acid suppression is a marker of increased risk of oesophageal and gastric adenocarcinoma. However, these associations are most likely explained by the underlying treatment indication being a risk factor for the cancer rather than an independent harmful effect of these agents per se.
Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension
Authors: G Rossi
Journal: Cardiovascular Research (2002)

Background: Endothelin (ET)-1 contributes to raising blood pressure (BP) and inducing cardiovascular disease by vasoconstriction and potent stimulation of aldosterone secretion. In the rat this latter effect occurs via ETB receptors; in humans in vitro studies implicated both ETA and ETB receptors, but there is no conclusive evidence in vivo. Methods: We recruited 13 consenting hypertensive patients: six with primary aldosteronism (PA) and seven with high-to-normal renin hypertension (HNRH). They were infused with a low dose (200 nmol/min for 5 min followed by 100 nmol/min for 10 min) of the ETA-selective antagonist BQ-123 either alone or, on a different day, together with an identical dose of the ETB-selective antagonist BQ-788. Plasma aldosterone, cortisol and ACTH concentration and plasma renin activity (PRA) were measured with radioimmunoassay at −15, 0, 30, 60, 120, 240, 360 min, while BP was recorded non-invasively. Results: BQ-123 alone and combined with BQ-788 significantly lowered mean BP in both PA and HNRH patients (by 6–10 mmHg at nadir; P<0.01). In PA patients, a short-lived decrease of aldosterone was elicited by combined BQ-123 and BQ-788 (−14%; P<0.05), but not by BQ-123 alone; cortisol, ACTH, and PRA were unaffected by either treatment. In HNRH patients, BQ-123 both alone and combined with BQ-788 lowered aldosterone (−39 and −28%, respectively) and PRA (−43 and −16%, respectively), while cortisol and ACTH were unaffected. Conclusions: Endogenous ET-1 contributes to maintaining the high BP values and the aldosterone secretion in both PA and HNRH patients. In the former patients, the aldosterone secretagogue effect of ET-1 is mediated via ETB receptors, while in the latter it occurs mainly via ETA-mediated stimulation of renin production.
Independence and Early American Hospitals, 1751-1812
Authors: William H. Williams
Journal: JAMA (1976)

John Adams once said that the American Revolution was complete in the minds of his countrymen before the Revolutionary War. St. John de Crevecoeur, a French immigrant to the United States during the 18th century, observed that the American was not a transplanted European, but "a new man who acts upon new principles...." If Adams and Crevecoeur were correct, this new and revolutionary man could be expected to conjure up new and unique medical institutions quite different from contemporary European models. But this was not the case. Indeed, the first genuine hospitals to be founded in the 13 colonies were transplanted British voluntary hospitals which found the climate and soil of the New World quite conducive to growth. The first enduring colonial institution to offer medical care to the sick was the almshouse. By the mid-18th century most of the leading ports in Anglo-America had constructed almshouses patterned after the
Metabolism of triglyceride-rich lipoproteins during alimentary lipemia.
Authors: F Karpe, G Steiner, T Olivecrona, L A Carlson, A Hamsten
Journal: Journal of Clinical Investigation (1993)

The metabolism of chylomicron remnants and VLDL was studied in healthy controls and normo- (NTG) and hypertriglyceridemic (HTG) patients with coronary artery disease after intake of an oral fat load. Specific determination of apo B-48 and B-100 enabled separation of the respective contribution of the two lipoprotein species. The postprandial plasma levels of small (Sf 20-60) and large (Sf 60-400) chylomicron remnants increased in controls and NTG patients. In contrast, only large chylomicron remnants increased in the HTG patients. An increase of large VLDL was seen in response to the oral fat load in all groups, whereas small VLDL were either unchanged in the controls and the NTG patients, or decreased in the HTG patient group. The whole plasma concentration of C apolipoproteins was essentially uninfluenced by the oral fat load, whereas the content in large triglyceride-rich lipoproteins paralleled the apo B elevations in controls and NTG patients. An even more prominent increase of apo B in large triglyceride-rich lipoproteins in the HTG group was not accompanied by an increase of C apolipoproteins. These findings indicate that chylomicrons compete with VLDL for removal of triglycerides by lipoprotein lipase and that the postprandial metabolism of triglyceride-rich lipoproteins is severely defective in hypertriglyceridemia.
OBESITY: AETIOLOGY AND METABOLISM
Authors: C. G. Lambie
Journal: BMJ (1935)

By obesity is meant an excessive accumulation of depot fat in the storage areas of the body.What constitutes excess will depend upon the point of view.The physiciani is called upon to regard obesity as a disfigurement, as a disease, or as a " sign."The aesthetic criteria of obesity may be determined by individual taste, or even by the dictates of fashion, but there comes a point at which the deposition of fat impairs functional activity and gives rise to symptoms, so that a person may be said to be too fat if the adiposity results in distress or discomfort of any kind, impairs the sense of well-being, or diminishes the capacity to enjoy life.Ultimately, by embarrassing the heart and respiration and diminishing the resistance to disease it may be a menace to life itself.Even where it does not itself produce any deleterious results, obesity may be a feature of various disorders, some of which may shorten life.The prognosis will depend upon the disease with which the obesity is associated.The correlation between obesity and the expectation of life is provided by insurance tables which indicate that, when a very large number of indi-viduals taken at random are examined, the expectation of life is diminished among those whose weight exceeds by a certain percentage the ibean of those individuals of the same height, age, and sex who have passed as first-class lives.It may be doubted, however, whether it is justifiable to assume that weight should increase with increasing age, as the insur- ance tables indicate.
10-6M (RR)-Formoterol, but Not (SS)-Formoterol or (S)/(R)-Albuterol, Inhibits RANTES Secretion by RSV Antigen-Stimulated Confluent Human Alveolar Epithelial Cells (cA549)
Authors: G. Puglisi, A. Capetandes, M. Frieri
Journal: Journal of Allergy and Clinical Immunology (2006)
Injectable Cell Constructs Fabricated via Culture on a Thermoresponsive Methylcellulose Hydrogel System for the Treatment of Ischemic Diseases
Authors: Chieh‐Cheng Huang, Zi‐Xian Liao, Ding‐Yuan Chen, Chun‐Wen Hsiao, Yen Chang, Hsing‐Wen Sung
Journal: Advanced Healthcare Materials (2014)

Cell transplantation via direct intramuscular injection is a promising therapy for patients with ischemic diseases. However, following injections, retention of transplanted cells in engrafted areas remains problematic, and can be deleterious to cell‐transplantation therapy. In this Progress Report, a thermoresponsive hydrogel system composed of aqueous methylcellulose (MC) blended with phosphate‐buffered saline is constructed to grow cell sheet fragments and cell bodies for the treatment of ischemic diseases. The as‐prepared MC hydrogel system undergoes a sol–gel reversible transition upon heating or cooling at ≈32 °C. Via this unique property, the grown cell sheet fragments (cell bodies) can be harvested without using proteolytic enzymes; consequently, their inherent extracellular matrices (ECMs) and integrative adhesive agents remain well preserved. In animal studies using rats and pigs with experimentally created myocardial infarction, the injected cell sheet fragments (cell bodies) become entrapped in the interstices of muscular tissues and adhere to engraftment sites, while a minimal number of cells exist in the group receiving dissociated cells. Moreover, transplantation of cell sheet fragments (cell bodies) significantly increases vascular density, thereby improving the function of an infarcted heart. These experimental results demonstrate that cell sheet fragments (cell bodies) function as a cell‐delivery construct by providing a favorable ECM environment to retain transplanted cells locally and consequently, improving the efficacy of therapeutic cell transplantation.
Urgent action is needed to prevent deaths among Himalayan pilgrims, says climbing federation
Authors: S. Yadav
Journal: BMJ (2009)

At least 10 pilgrims have died over the past three weeks while visiting the Kailash Manasarovar area in Tibet, which is at an altitude of over 4500 m. The medical commission of the International Mountaineering and Climbing Federation has called for urgent action to prevent the deaths.

The pilgrims are said to have died of altitude related illnesses and worsening of other conditions. Dozens of other pilgrims with serious altitude related illnesses had to be rescued by helicopter.

The area, believed to be the abode of the …