tbuckley/cabot-search huggingface dataset:
NHS England announces 29 sites to spearhead integrated care models
Authors: G. Iacobucci
Journal: BMJ (2015)

The NHS has chosen the first 29 “vanguard” sites across England to adopt new models of integrated healthcare.

The selected geographical areas will take the lead nationally on developing the new care models proposed in NHS England’s Five Year Forward View ,1 including multispecialty community providers (MCPs), designed to move specialist care out of hospitals into the community, and integrated primary and acute care systems (PACs) that join up GP, hospital, community, and mental health services.

Other sites will adopt new models of enhanced healthcare in care homes designed to offer older people better, joined-up health, care, and rehabilitation services.

The vanguard sites will receive tailored national support packages from NHS England from April 2015 and will be able to use the government’s £200m (€280m; $300m) transformation fund. The fund will not be apportioned evenly between sites but will instead be available according to the …
Pulmonary Cryptococcal Granulomas
Authors: Rick M Fairhurst, David A Pegues
Journal: New England Journal of Medicine (2002)

Figure 1. A 48-year-old man with diabetes mellitus underwent pancreas–kidney transplantation for end-stage renal disease. One month later, he was treated for rejection, and computed tomography of the chest showed no pulmonary infiltrates. Nine months after transplantation, cryptococcal meningitis developed. He received intravenous amphotericin B–lipid complex, and long-term therapy with oral fluconazole was begun. The serum cryptococcal antigen titer was 1:512 and decreased to undetectable levels over a period of five years. Six years after transplantation, progressive renal-allograft failure developed. A chest radiograph showed multiple nodules confined to the left lung. The patient had no fever and no pulmonary symptoms. . . .
Absence Seizures Associated With Bicarbonate Therapy and Normal Serum pH
Authors: Shimon Reif
Journal: JAMA (1989)

<h3>To the Editor.—</h3> Renal tubular acidosis is known to cause failure to thrive.<sup>1,2</sup>We found that treating children with this condition by oral administration of sodium bicarbonate is both beneficial and benign. <h3>Report of a Case.—</h3> A 2 1/2-year-old girl with failure to thrive and weight and height below the third percentile for her age was referred to our department. Extensive investigation revealed metabolic acidosis (pH, 7.3 to 7.33), with hypocarbonemia of 16 to 18 mEq/L and hyperchloremia of 116 to 117 mmol/L. After excluding other causes, a presumptive diagnosis of renal tubular acidosis was made and oral therapy with 4 mEq/kg per day of sodium bicarbonate was instituted. This raised her blood pH level to 7.41 to 7.43 and enabled the child to attain the 10th percentile of weight and height for her age. A month later, the child experienced four episodes of absencelike seizures. There was no
The dissimilar siblings or: the NFAT-modulated yin and yang of AIF-1 and IRT-1 in cardiovascular diseases
Authors: P. Stieger, R. C. Braun-Dullaeus
Journal: Cardiovascular Research (2012)

This editorial refers to ‘NFAT regulates the expression of AIF-1 and IRT-1: yin and yang splice variants of neointima formation and atherosclerosis’ by L.M. Berglund et al ., pp. 414–423, this issue. 

In cardiovascular medicine, post-interventional activity of vascular smooth muscle cells (VSMC) certainly is one of the crucial determinants of clinical success or failure of therapeutic attempts. It is this peculiar character of the VSMC reaction that plays a key role in the pathogenesis of procedurally initiated diseases such as restenosis after angioplasty, in-stent restenosis, allograft arteriopathy, or vascular bypass graft occlusion.1 A common feature of these vascular pathological processes is neointimal proliferation. There is an abundant variety of contributors to these vascular pathologies described in the current literature that provides distinct evidence for a main cast of growth factors and cytokines produced by injured endothelium and inflammatory cells that activate the normally quiescent VSMC.2 Still, identification of novel molecular mechanisms that regulate VSMC migration and proliferation in response to injury and inflammation raises hopes for resolution of the continuing drama of post-interventional failure.

Along these lines, Berglund et al. 3 focus on quite a familiar group of suspects. The effects of nuclear factor of activated T cells (NFAT), an immune response factor, were tested whose role in neointima formation has been successfully …
Coronary patency, infarct size and left ventricular function after thrombolytic therapy for acute myocardial infarction: results from the tissue plasminogen activator: Toronto (TPAT) placebo-controlled trial
Authors: Christopher D Morgan, Robin S Roberts, Aminul Haq, Ronald S Baigrie, Paul A Daly, Michael Gent, Paul W Armstrong
Journal: Journal of the American College of Cardiology (1991)
A Premature Infant With H-Type Tracheoesophageal Fistula Demonstrated by Scintigraphic Technique
Authors: ??lfet Vatansever, Bet??l Acuna&OV0613;, Tansu Salman, G??lay Altun, Rdvan Duran
Journal: Clinical Nuclear Medicine (2006)

Purpose: Congenital tracheoesophageal fistula (TEF) without esophageal atresia is commonly known as "H" type. This is extremely rare in infants. The rarity of the condition, its nonspecific symptomatology, and limitations in its demonstration by contrast radiology and endoscopy contribute to delays between first presentation and confirmation of the diagnosis. Our aim was to demonstrate a congenital H-type tracheoesophageal fistula by using Tc-99m sulfur colloid scintigraphy. Materials and Methods: A case report. Results: A preterm female infant was born by cesarean section at 34 weeks gestation. After many attempts of feeding, she developed apnea, resolving spontaneously, peroral cyanosis, pallor, hypersalivation, and abdominal distension, even when she was being fed by an orogastric tube. With this complex symptomatology, she was suspected to have an H-type TEF. Because of prematurity and recurrent respiratory problems of the infant and the high risk of aspiration of contrast material during a cineradiographic procedure, and also because of the invasive nature of the endoscopic procedure as well as the requirement of general anesthesia, the diagnosis was made by using Tc-99m sulfur colloid scintigraphy and confirmed at operation. Conclusion: Demonstrating a congenital H-type tracheoesophageal fistula by using radionuclide imaging is an easily applicable technique.
Metabolic and renal clearance rates of purified human chorionic gonadotropin.
Authors: R E Wehmann, B C Nisula
Journal: Journal of Clinical Investigation (1981)

The metabolic clearance rate (MCR) and renal clearance rate (RCR) of human chorionic gonadotropin (hCG) were measured in healthy young men and women using techniques of continuous intravenous infusion and rapid intravenous injection of unlabeled, highly purified hCG. Seven subjects received 4 d of infusion at a rate of 0.2 microgram/min, followed by an additional 4 d of infusion at 0.8 microgram/min. Mean serum levels of hCG established at these rates of infusion were 61.1 +/- 3.3 and 237 +/- 16 ng/ml, respectively (mean +/- SEM). The MCR determined at the low infusion rate was not significantly different from that determined at the higher infusion rate (1.83 +/- 0.09 vs. 1.95 +/- 0.14 ml/min per m2). The mean MCR for all subjects was 1.88 +/- 0.08 ml/min per m2. The MCR was not significantly different between men amd women (2.04 +/- 0.13 vs. 1.76 +/- 0.07 ml/min per m2). The RCR also did not vary between low and high infusion rates (0.40 +/- 0.03 vs. 0.40 +/- 0.04 ml/min per m2). The mean RCR for all subjects was 0.40 +/- 0.02 ml/min per m2. There was no difference in RCR between men and women (0.42 +/- 0.05 vs. 0.39 +/- 0.03 ml/min per m2). Six subjects were given 1.0 mg of highly purified hCG by rapid intravenous injection. Initial serum levels of hCG were 300-400 ng/ml, and the subsequent disappearance curve was multiexponential over 8-10 d. The disappearance curve of hCG in each subject was fitted to a biexponential equation. The rapid component t1/2 was 5.97 +/- 0.63 h and the slow component t1/2 was 35.6 +/- 8.0 h. We conclude that the MCR of purified hCG in man is about 2 ml/min per m2 and the RCR is 0.4 ml/min per m2; these parameters are concentration independent and do not differ significantly between healthy young men and women.
Metabolism and possible health effects of aluminum.
Authors: P O Ganrot
Journal: Environmental Health Perspectives (1986)

Literature regarding the biochemistry of aluminum and eight similar ions is reviewed. Close and hitherto unknown similarities were found. A hypothetical model is presented for the metabolism, based on documented direct observations of Al3+ and analogies from other ions. Main characteristics are low intestinal absorption, rapid urinary excretion, and slow tissue uptake, mostly in skeleton and reticuloendothelial cells. Intracellular Al3+ is probably first confined in the lysosomes but then slowly accumulates in the cell nucleus and chromatin. Large, long-lived cells, e.g., neurons, may be the most liable to this accumulation. In heterochromatin, Al3+ levels can be found comparable to those used in leather tannage. It is proposed that an accumulation may take place at a subcellular level without any significant increase in the corresponding tissue concentration. The possible effects of this accumulation are discussed. As Al3+ is neurotoxic, the brain metabolism is most interesting. The normal and the lethally toxic brain levels of Al3+ are well documented and differ only by a factor of 3-10. The normal brain uptake of Al3+ is estimated from data on intestinal uptake of Al3+ and brain uptake of radionuclides of similar ions administered intravenously. The uptake is very slow, 1 mg in 36 years, and is consistent with an assumption that Al3+ taken up by the brain cannot be eliminated and is therefore accumulated. The possibility that Al3+ may cause or contribute to some specific diseases, most of them related to aging, is discussed with the proposed metabolic picture in mind.
Transcription syndromes and the role of RNA polymerase II general transcription factors in human disease.
Authors: T Aso, A Shilatifard, J W Conaway, R C Conaway
Journal: Journal of Clinical Investigation (1996)

Messenger RNA synthesis is a major site for the regulation of gene expression. Eukaryotic messenger RNA synthesis is catalyzed by multisubunit RNA polymerase II (1–3) and proceeds via multiple stages, which are designated preinitiation, initiation, elongation, and termination and which have come to be referred to collectively as the transcription cycle (Fig. 1). The past decade was a watershed for biochemical studies of eukaryotic messenger RNA synthesis. A diverse collection of transcription factors and other nuclear proteins that govern the activity of RNA polymerase II during messenger RNA synthesis was identified and characterized, and unprecedented progress in several key research areas has provided a deeper understanding of the biochemical mechanisms underlying many aspects of eukaryotic transcriptional regulation. First, major breakthroughs in investigations of the structures of eukaryotic protein-coding genes and the role of chromatin in the regulation of their expression were achieved. Chromatin proteins, such as histones and HMG proteins, were found to play crucial roles in gene regulation by packaging genes into inactive or transcriptionally repressed configurations (4–9). Second, many DNA binding transactivators that interact specifically with upstream promoter elements and enhancer sequences located in the promoter-regulatory regions of genes were isolated, classified according to their structures, and found to regulate the expression of specific genes or gene families by controlling the rate of initiation (10) and, as shown more recently, the efficiency of elongation by RNA polymerase II (11–13). Third, chromatin remodeling proteins, such as the multisubunit SWI/SNF (14, 15) and NURF (16, 17) complexes, were discovered and found to play key roles in transcriptional activation by promoting conversion of regions of inactive chromatin into transcriptionally active, open chromatin, thereby allowing DNA binding transactivators and RNA polymerase II access to the promoter-regulatory regions of genes (4, 18–23). Fourth, coactivators, such as the SRB-containing mediator complex (2, 3, 24, 25), CREB binding protein (CBP) 1
Binding and internalization of transforming growth factor-β1 by human hepatoma cells: Evidence for receptor recycling
Authors: Kim A. Sathre, Monica L.-S. Tsang, James A. Weatherbee, Clifford J. Steer
Journal: Hepatology (1991)

Cellular processing of 125I-labeled transforming growth factor-beta 1 was investigated in the human hepatoma cell lines Hep G2 and Hep 3B. Binding of 125I-transforming growth factor-beta 1 to cell surface receptors was specific, saturable and calcium-independent. Both cell lines exhibited a single class of high-affinity (Kd = 2.2 x 10(-10) mol/L) binding sites (4.5 x 10(3) for the Hep G2 cell; 1.5 x 10(3) for the Hep 3B cell) for both human and porcine transforming growth factor-beta 1. Binding was temperature dependent, time dependent and pH dependent. Cell-bound 125I-transforming growth factor-beta 1 was removed by brief exposure to acidic medium (pH less than 4) but was converted into an acid-resistant state rapidly after shifting the cells to 37 degrees C. Spontaneous dissociation of bound ligand over a 6 hr period at 4 degrees C was less than 10%. Disuccinimidyl suberate was used to covalently label 125I-transforming growth factor-beta 1 to cell-surface binding sites. Labeling of the ligand/receptor complexes was inhibited by unlabeled transforming growth factor-beta 1 but was unaffected by other growth factors. The radiolabeled complexes showed approximate molecular weights of 280,000, 85,000 and 65,000 when run on reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cell-bound 125I-transforming growth factor-beta 1 was internalized and degraded at 37 degrees C, and the products were released into the medium as trichloroacetic acid-nonprecipitable radioactivity. The lysosomotropic base chloroquine and the carboxylic ionphore monensin inhibited degradation and release of 125I-labeled products from the cells.(ABSTRACT TRUNCATED AT 250 WORDS)
A Call to Recognize PCP
Authors: Zenonas Danilevicius
Journal: JAMA (1975)

We are tough and hardened men. The influence of Women's Liberation does not permit us to tip our hats to a lady. However, we respond to the smile of an innocent baby; and if ever compassion is felt in our hearts, it is especially poignant when we see a suffering or dying child. Our profession, dedicated to saving lives, has largely eliminated sentiment from our work. However, when a child's life is at stake, a physician will, with emotion, do all he can to save it.  One of the worst, fastest-moving, and cruelest killers of children is Pneumocystis carinii pneumonia (PCP). This syndrome seldom develops in a strong, well-nourished child with an uncompromised immune system. However, children in the first year of life, who are malnourished or who have debilitating diseases or malignancy and whose immunologic status is compromised, are especially vulnerable. In the United States, the disease is less
The Alarmin HMGN1 Contributes to Antitumor Immunity and Is a Potent Immunoadjuvant
Authors: Feng Wei, De Yang, Poonam Tewary, Yana Li, Sandra Li, Xin Chen, O.M. Zack Howard, Michael Bustin, Joost J. Oppenheim
Journal: Cancer Research (2014)

Abstract Alarmins are endogenous mediators that are elicited rapidly in response to danger signals, enhancing innate and adaptive immune responses by promoting the recruitment and maturation of antigen-presenting cells (APC). The nucleosome-binding protein HMGN1 is a potent alarmin that binds TLR4 and induces antigen-specific Th1 immune responses, but its contributions to antitumor immunity have not been explored. We found that ovalbumin (OVA)-expressing EG7 mouse thymoma cells grew much faster in Hmgn1-deficient mice than littermate-matched controls. Tumor-bearing Hmgn1−/− mice generated fewer OVA-specific CD8 cells in the spleen than EG7-bearing Hmgn1+/+ mice, suggesting that HMGN1 supported T cell–mediated antitumor immunity. In addition, EG7 tumors expressing HMGN1 grew more slowly than control EG7 tumors, suggesting greater resistance to HMGN1-expressing tumors. This resistance relied on T cell–mediated immunity because it was abolished by in vivo depletion of CD4+ and CD8+ T cells. Moreover, mice vaccinated with a DNA vector expressing an HMGN1–gp100 fusion protein manifested gp100-specific, Th1-polarized immune responses, acquiring resistance to challenge with mouse B16F1 melanoma. Overall, our findings show that HMGN1 contributes to antitumor immunity and it may offer an effective adjuvant to heighten responses to cancer vaccines. Cancer Res; 74(21); 5989–98. ©2014 AACR.
Armed Antibodies Targeting the Mucin Repeats of the Ovarian Cancer Antigen, MUC16, Are Highly Efficacious in Animal Tumor Models
Authors: Youjun Chen, Suzanna Clark, Terence Wong, Yongmei Chen, Yvonne Chen, Mark S. Dennis, Elizabeth Luis, Fiona Zhong, Sheila Bheddah, Hartmut Koeppen, Alvin Gogineni, Sarajane Ross, Paul Polakis, William Mallet
Journal: Cancer Research (2007)

Abstract MUC16 is a well-validated cell surface marker for serous adenocarcinomas of the ovary and other gynecologic malignancies that is distinguished by highly repetitive sequences (“mucin repeats”) in the extracellular domain (ECD). We produced and compared two monoclonal antibodies: one (11D10) recognizing a unique, nonrepeating epitope in the ECD and another (3A5) that recognizes the repeats and binds multiple sites on each MUC16 protein. 3A5 conjugated to cytotoxic drugs exhibited superior toxicity against tumor cells in vitro and in tumor xenograft models compared with antibody-drug conjugates of 11D10. Importantly, drug conjugates of 3A5 were well tolerated in primates at levels in excess of therapeutic doses. Additionally, the presence of circulating CA125 in a rat model did not exacerbate the toxicity of 3A5 drug conjugates. We conclude that targeting the repeat MUC16 domains, thereby increasing cell-associated levels of drug-conjugated antibody, provides superior efficacy in vitro and in vivo without compromising safety. [Cancer Res 2007;67(10):4924–32]
Independence of Serum Lipid Levels and Dietary Habits
Authors: Allen B. Nichols
Journal: JAMA (1976)

Serum cholesterol and triglyceride levels were correlated with dietary habits of 4,057 adult participants in a prospective epidemiologic survey of cardiovascular disease in Tecumseh, Mich. Frequency of consumption of 110 different food items was determined for each participant and average weekly consumption rates of foods high in fat, sugar, starch, and alcohol content were calculated. Frequency of consumption of these nutrients was then correlated with serum cholesterol and triglyceride levels of individual subjects. Serum cholesterol and triglyceride values were not positively correlated with selection of dietary constituents. Positive correlations between serum lipid levels and adiposity were statistically significant. These findings suggest that serum cholesterol and triglyceride levels among Americans are more dependent on degree of adiposity than on frequency of consumption of fat, sugar, starch, or alcohol. (<i>JAMA</i>236:1948-1953, 1976)
In the Magic Mirror
Authors: M. Therese Southgate
Journal: JAMA (2007)

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ABC of blood pressure management.
Authors: P Semple
Journal: BMJ (1981)

parenteral fluids include septicaemia, hepatocellular damage, renal impairment, and any degree ofacidosis.Patients requiring parenteral nutrition commonly fulfil such criteria.Secondly, all preparations mentioned in the British National Formulary 1981 as containing ethanol also contain either sorbitol or laevulose, the metabolism of which produces glyceralde- hyde 3-phosphate.If gluconeogenesis is reduced by simultaneous metabolism of ethanol then the only pathway available is conversion of glyceraldehyde to lactate.:'The use of such preparations will result in both overproduction and underutilisation of lactate and therefore increased risk of lactic acidosis.The use of glucose as a source of calories in parenteral feeding is easier to monitor since blood glucose measurements with Dextrostix and a suitable meter are more readily available than measurements of blood lactate.
Platelet-derived growth factors enhance proliferation of human stromal stem cells
Authors: Enrico Lucarelli, Amira Beccheroni, Davide Donati, Luca Sangiorgi, Annarita Cenacchi, Anna M. Del Vento, Carolina Meotti, Annarosa Zambon Bertoja, Roberto Giardino, Pier M. Fornasari, Mario Mercuri, Piero Picci
Journal: Biomaterials (2003)
Direct visualization of the focus of ventricular premature contraction by high-speed digital subtraction echography
Authors: Ken Ishihara, Jun Tanouchi, Akira Kitabatake, Masaaki Uematsu, Tohru Masuyama, Yasuji Doi, Takenobu Kamada, Shinji Kishimoto
Journal: Journal of the American College of Cardiology (1991)
New breast screening leaflet still denies women the full picture, says critic
Authors: Z. Kmietowicz
Journal: BMJ (2013)

The new breast cancer screening leaflet for UK women, updated last week after widespread consultation, still fails to spell out the true risks of mammography and denies women the chance to make a properly informed choice, a critic of the NHS’s screening information has said.

Susan Bewley, professor of complex obstetrics at King’s College London, told the BMJ that the leaflet does not contain crucial information derived by an independent panel last year: that for every 15 women who are given a diagnosis through screening and who will undergo treatment, only one life will be saved and three women will have been treated unnecessarily. Although the leaflet mentions overdiagnosis, it does not explain the harms of screening and overlooks the increased chance of mastectomy, she said. …