tbuckley/cabot-search huggingface dataset:
Interleukin 2 receptor gamma chain expression on resting and activated lymphoid cells.
Authors: T Nakarai, M J Robertson, M Streuli, Z Wu, T L Ciardelli, K A Smith, J Ritz
Journal: The Journal of Experimental Medicine (1994)

The interleukin 2 receptor (IL-2R) is known to be comprised of at least three genetically distinct subunits termed alpha, beta, and gamma. These chains can be expressed individually or in various combinations resulting in distinct receptors with different affinities for IL-2. In contrast to alpha and beta, the cell surface expression of the gamma chain protein previously has not been well-characterized. To examine cell surface expression of IL-2R gamma on hematopoietic cells, we developed two new monoclonal antibodies (mAbs) specific for this protein. Both 1A11 (immunoglobulin [IgG1]) and 3G11 (IgM) specifically reacted with murine cells transfected with IL-2R gamma cDNA, and immunoprecipitation studies indicated that both antibodies precipitated a protein of approximately 62-65 kD. Scatchard analysis of IL-2 binding to murine cells transfected with cDNA-encoding combinations of IL-2R components demonstrated that neither beta nor gamma chain bind IL-2 with measurable affinity, but coexpression of both beta and gamma is sufficient to form an intermediate affinity receptor. In the absence of gamma chain, beta chain interacts with alpha chain to form a "pseudo-high" affinity receptor. In contrast, gamma chain does not appear capable of interacting with alpha in the absence of beta chain. Thus, gamma chain appears to interact only with beta, but beta chain is capable of interacting with both alpha and gamma. Using the newly developed mAbs to examine cell surface expression by immunofluorescence, resting T cells were found to express low levels of gamma chain without detectable alpha or beta. Early after mitogen stimulation, T cells expressed higher levels of alpha, beta, and gamma. However, at later time points, T cells expressed alpha and gamma in marked excess over beta. Thus, formation of high affinity IL-2R on activated T cells was primarily limited by beta chain expression. In contrast, resting natural killer (NK) cells constitutively expressed IL-2R beta without detectable alpha or gamma. After activation with either IL-2 or IL-12, expression of both alpha and gamma transiently increased and then returned to very low levels. Expression of functional IL-2R on resting and activated NK cells, therefore, appeared to be primarily limited by the expression of gamma chain. IL-2 binding studies with resting NK cells confirmed the results of immunofluorescence studies indicating the presence of very low numbers of intermediate affinity (beta gamma) receptors for IL-2 on these cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Trading regulations and health foods
Authors: M E J Lean
Journal: BMJ (2008)

New legislation requires evidence for marketed health foods

The European Union promotes a free market economy in Europe; however, the pursuit of profit sometimes has to be curtailed if consumers are injured or deceived. For example, the unregulated marketing of certain foods may include claims about effects on health that deceive patients. The EU Directive on Unfair Commercial Practices, enforced in the United Kingdom in May 2008,1 was designed “to plug gaps in existing consumer protection legislation” and “to protect vulnerable consumers who are often the target of unscrupulous traders.” It obliges businesses not to mislead consumers,2 and this includes health claims for services or products.

The distinction between medicines and foods is sometimes unclear when they are marketed for health reasons, and consumers can be misled. Medicines are licensed in Europe only after stringent experimental research to establish safety and efficacy. In the UK, this process is regulated by the Medicines and Healthcare …
Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes
Authors: Yaakov Nahmias, Monica Casali, Laurent Barbe, Francois Berthiaume, Martin L. Yarmush
Journal: Hepatology (2006)

Low-density lipoprotein (LDL) is an important carrier of plasma cholesterol and triglycerides whose concentration is regulated by the liver parenchymal cells. Abnormal LDL regulation is thought to cause atherosclerosis, while viral binding to LDL has been suggested to facilitate hepatitis C infection. Primary hepatocytes quickly lose the ability to clear LDL during in vitro culture. Here we show that the coculture of hepatocytes with liver sinusoidal endothelial cells (LSEC) significantly increases the ability of hepatocytes to uptake LDL in vitro. LDL uptake does not increase when hepatocytes are cocultured with other cell types such as fibroblasts or umbilical vein endothelial cells. We find that LSECs induce the hepatic expression of the LDL receptor and the epidermal growth factor receptor. In addition, while hepatocytes in single culture did not take up hepatitis C virus (HCV)-like particles, the hepatocytes cocultured with LSECs showed a high level of HCV-like particle uptake. We suggest that coculture with LSECs induces the emergence of a sinusoidal surface in primary hepatocytes conducive to the uptake of HCV-like particles. In conclusion, our findings describe a novel model of polarized hepatocytes in vitro that can be used for the study of LDL metabolism and hepatitis C infection.
Reduced thymus activity and infection prematurely age the immune system
Authors: Ronald E. Gress, Steven G. Deeks
Journal: Journal of Clinical Investigation (2009)

The aging process affects all aspects of the immune system, particularly the T cells. The immune system in older individuals is often characterized by lower T cell numbers, lower naive/memory T cell ratios, and lower T cell diversity. Most measures of inflammation increase with age. Why this happens, and why there is so much person-to-person variability in these changes, is not known. In this issue of the JCI, Sauce and colleagues show that removal of the thymus during infancy results in premature onset of many of these age-associated changes to the immune system (see the related article beginning on page 3070). The effect of thymectomy was particularly notable in those individuals who acquired CMV infection. Data from this study, as well as data from other observational settings, suggest that reduced thymic function and persistent viral infections combine to accelerate a decline in immunologic function.
Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells
Authors: Susobhan Sarkar, Axinia Doring, Franz J Zemp, Claudia Silva, Xueqing Lun, Xiuling Wang, John Kelly, Walter Hader, Mark Hamilton, Philippe Mercier, Jeffery F. Dunn, Dave Kinniburgh, Nico van Rooijen, Stephen Robbins, Peter Forsyth, Gregory Cairncross, Samuel Weiss, V Wee Yong
Journal: Nature Neuroscience (2013)
THE TEMPERATURE AND SATURATION OF EXHALED AIR IN RELATION TO CATARRHAL INFECTIONS
Authors: P. Tozer
Journal: BMJ (1924)

A lowering of the energy expenditure under quinine thus occurred in onlly a very small proportion of cases, and even in these the effects did not last for quite three hours.To economize materially the energy expenditure would thus involve the repetition of the full pliarmacopoeial doses (0.6 gram quinine hydrochloride for the adult) at intervals of aboi;t three hours.Even this heroic treatment might well Iail to maintain the effect, and the other symptoms from such doses would certainly be undesirable; it is thus not practicable to attain any conisidelable saving of energy through quinine in a prolonged febrile illness.I have not laid any stress upon the extent of temperature reduction, for it is not so important in itself, ancd it is well recognized that quinine is not as good an antipyretic in nion-malarial as in malarial fevers.We have already a large mass of evideniee to disprove the location of its action in the tissues.It lhas, accordingto Feri,16 no effect, prevenitive or curative, upon the fever caused by tetrahydro-beta-niaphthylaimiine, wlhich acts centrally.Senta'7 founid that while it is capable of reducing the oxygen used by muscular tissue in vitro, the conicentration required to effect this (1 in 5,000 or higher) is much hiigher than that attained by a therapeutic dose.Lastly, and most illmportant of all, Barbour and WA'ingl8 have showni that direct application of quininie to the lheat centres causes a certain amounit of aiitipyresis.CONCLUSIONS.1. Quinine does not differ in.its mode of action from other antipyretic drugs.2. It has nio action on the protein metabolism in lhealth.3. It does not reduce the gaseous exchanige and.heat production except in a small proportion of fever cases, and even in these the action lasts for less than three hours with the maximum pharmacopoeial doses. 4. It is not possible in non-malarial fevers to attain a saving of energy and tissue destruction through quininie.This work was rendered possible onily tlhrouglh the kind lhelp of many in the laboratories and clinics.I must content myself here with expressing my deep obligationi to them all.
UNPERFORATED ULCERS OF TERMINAL ILEUM, SYMPTOMATICALLY SIMULATING APPENDICITIS
Authors: J. SHELTON HORSLEY
Journal: JAMA (1925)

As Hertzler has remarked, it seems strange that a viscus capable of such a wide range of locality as the appendix will, when inflamed, always have a point of greatest tenderness over the so-called McBurney's point, about midway between the right anterior superior spinous process of the ilium and the navel. He says the answer is that it does not. While the normally placed appendix gives pain at this point, the appendix abnormally situated shows maximum pain and tenderness elsewhere. The symptoms of a typical uncomplicated case of acute appendicitis permit little diagnostic doubt. The rather sudden pain beginning in the epigastrium or around the navel, and the general abdominal discomfort with pain and muscle spasm eventually settling in the right iliac fossa, are almost pathognomonic of appendicitis. The sequence of the pain in the epigastrium or around the navel and later in the right iliac fossa is important. These
Dynamic changes in the zone of apposition and diaphragm length during maximal respiratory efforts.
Authors: D K McKenzie, S C Gandevia, R B Gorman, F C Southon
Journal: Thorax (1994)

BACKGROUND--Clinical tests of diaphragmatic strength are limited by the wide normal variation in maximal pressure which result, in part, from changes in diaphragmatic length. During relaxation at different lung volumes diaphragmatic length (LDI) can be estimated from the length of the zone of apposition (LZapp) and the transverse diameter of the rib cage (DRC). A study was carried out in two subjects using sequential digital radiography at six frames/second to determine whether these relations apply during maximal respiratory efforts which distort the rib cage and diaphragm. METHODS--The length of the anteroposterior contour of the diaphragm and DRC were determined by curve fitting. LZapp was measured with a millimetre rule. RESULTS--A significant correlation was found between LDI and LZapp during both maximal inspiratory and expulsive manoeuvres (R2 = 0.88 and 0.52). LDI was estimated from the measurements of LZapp and DRC using a multiple regression equation derived from measurements during static relaxation. Despite the complex dynamic events at the onset of these "static" manoeuvres, actual LDI correlated strongly with derived LDI using all data for the two manoeuvres in each subject (R2 = 0.95 and 0.84). Measurements with ultrasonography (12 cm linear probe) and magnetometers confirmed the changes in LZapp and DRC during inspiratory and expulsive efforts. CONCLUSIONS--Non-invasive measurements of LZapp and DRC can be used to derive an accurate estimate of diaphragmatic length under dynamic conditions.
A rare cause of obscure gastrointestinal bleeding
Authors: J. W. Chou
Journal: Gut (2010)

A 43-year-old man presented to our hospital because of a 1 day history of melaena. On admission, physical examination was unremarkable. His haemoglobin was 11.5 g/dl. Oesophagogastroduodenoscopy and colonoscopy disclosed no evidence of a bleeding lesion. Capsule endoscopy (CE) demonstrated …
Hyperpyrexia during anaesthesia.
Authors: P. J. Horsey
Journal: BMJ (1968)

7 September, p. 597) suggests that "the term drowning should be used to denote the process resulting from submersion in water in which there is loss of conscious- ness and threat to life."Within the com- mon use of "drowning" and the above definition of the term there is an elision,- immersion hypothermia.Keatingel showed in the Lakonia disaster that " hypothermia led to the deaths of most, perhaps as many as 113 out of 124 who died."He has also stated that "approximately 1,000 people die from immersion in British coastal and inland waters every year.
Satisfaction with out of hours primary care
Authors: N. Walker, R. Baker
Journal: BMJ (2015)

Time to stop writing reports and start taking action

In November 2014, the House of Commons Committee of Public Accounts concluded that patients’ experience of primary care out of hours in England varies considerably and unacceptably across the country, as does the cost.1 The committee criticised NHS England for its failure to provide effective oversight and, among other recommendations, urged NHS England to develop its understanding of reasons for the variations in experience and costs. In the July 2014 GP Patient Survey, 66% of respondents rated their overall experience of out of hours care as “very good” or “good,” but the trend is downwards, the respective ratings being 68% in December 2013 and 71% in December 2012.2 Providing evidence that NHS England will find helpful, a linked paper by Warren and colleagues (doi:10.1136/bmj.h2040) analyses results of the national GP Patient Survey and describes factors associated with poor patient experience of out of hours services.3

In recent years various steps have been taken to improve out of hours care. In 2006 the Department of Health published several National Quality Requirements that out of hours providers are obliged to meet.4 In 2010, after a series …
Disruption of the Diurnal Rhythm of Plasma Melatonin in Cirrhosis
Authors: Petra E. Steindl, Barry Finn, Bernard Bendok, Steven Rothke, Phyllis C. Zee, Andres T. Blei
Journal: Annals of Internal Medicine (1995)

Objectives: To assess 24-hour plasma melatonin profile as a marker of output rhythm from the circadian clock and to study sleep diaries as reflections of subjective sleep quality in patients with liver cirrhosis. Design: Prospective cohort study. Setting: Clinical research center in a university hospital. Patients: Seven patients with cirrhosis but not alcoholism and seven age-, sex-, and education-matched controls. Measurements: Neuropsychological testing to confirm subclinical hepatic encephalopathy. Plasma melatonin levels measured every 30 minutes for 24 hours by radioimmunoassay. Sleep diaries kept for 1 week before admission. Results: Patients with cirrhosis had markedly elevated melatonin levels during daytime hours; in addition, the time of onset of melatonin increase and the time at which melatonin levels peaked were consistently and significantly delayed in these patients. Sleep diaries indicated more nocturnal awakenings and more frequent daytime naps in patients with cirrhosis. Conclusion: Disruption of the diurnal rhythm of melatonin may reflect alterations of circadian function that could contribute to the disturbances of the sleep-wake cycle frequently seen in patients with cirrhosis.
Abstract 2619: Whole genome and transcriptome sequencing identifies an activating mutation of <i>LPAR1</i> in a patient with metastatic neuroblastoma.
Authors: Jun S. Wei, Peter Johansson, Li Chen, Young K. Song, Catherine Tolman, Samuel Li, Laura Hurd, Rajesh Patidar, Xinyu Wen, Thomas C. Badgett, Adam Cheuk, Jean-Claude Marshall, Patricia Steeg, José Pedro Vaqué Díez, J Silvio Gutkind, Javed Khan
Journal: Cancer Research (2013)

Abstract Neuroblastoma is the most common extra-cranial solid tumor of childhood, and is one of the most genomically heterogeneous malignances studied to date. Despite advance of multimodal therapies, the current overall survival rate for patient with metastatic neuroblastoma is &amp;lt;40%, and the molecular events that drive the disease are not fully understood. To systematically identify expressed driver oncogenes, we performed whole genome and transcriptome sequencing on an index liver metastasis of neuroblastoma from a young adult patient. Additional transcriptome sequencing was performed on tumor cells from bone marrow taken at diagnosis and from the adrenal primary taken at the time of primary surgical resection. Whole genome sequencing of the index tumor identified 44 somatic small variant mutations in 42 genes and a large hemizygous deletion in the ATRX gene which has been recently implicated in neuroblastoma. Of these 45 somatic alterations, 15 genes including ATRX were found commonly mutated in all three tumors and transcriptome sequencing showed 3 of them (LPAR1, GATA2, and NUFIP1) had high level of expression of the mutant alleles, suggesting potential oncogenic driver roles for these mutated genes. Among these commonly mutated expressed genes, the druggable G-protein coupled receptor LPAR1 was expressed at the highest level in all tumors. Cells expressing the LPAR1 mutant resulted in a significant increase in motility, but had no effect on growth. Further biochemical characterization demonstrated that elevated Rho signaling was responsible for the increased cell mobility mediated by the LPAR1 mutant. Therefore, parallel whole genome and transcriptome sequencing identified a cell motility driver mutation in the LPAR1 gene, and this combinatorial approach may be leveraged for identification of expressed driver mutations in cancer patients for precision therapy. Citation Format: Jun S. Wei, Peter Johansson, Li Chen, Young K. Song, Catherine Tolman, Samuel Li, Laura Hurd, Rajesh Patidar, Xinyu Wen, Thomas C. Badgett, Adam Cheuk, Jean-Claude Marshall, Patricia Steeg, José Pedro Vaqué Díez, J Silvio Gutkind, Javed Khan. Whole genome and transcriptome sequencing identifies an activating mutation of LPAR1 in a patient with metastatic neuroblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2619. doi:10.1158/1538-7445.AM2013-2619
The Actin-Binding Protein Girdin and Its Akt-Mediated Phosphorylation Regulate Neointima Formation After Vascular Injury
Authors: Hiroshi Miyake, Kengo Maeda, Naoya Asai, Rei Shibata, Hitoshi Ichimiya, Mayu Isotani-Sakakibara, Yumiko Yamamura, Katsuhiro Kato, Atsushi Enomoto, Masahide Takahashi, Toyoaki Murohara
Journal: Circulation Research (2011)

Rationale: It is well established that the migration and proliferation of vascular smooth muscle cells (VSMCs) have major roles in the vascular remodeling process. Our previous study showed that the Akt substrate Girdin, which is expressed in VSMCs and endothelial cells, is essential for postnatal angiogenesis. However, the function of Girdin and its Akt-mediated phosphorylation in VSMCs and their in vivo roles in vascular remodeling remain to be elucidated. Objective: We investigated the function of Girdin and its Akt-mediated phosphorylation using cultured VSMCs and animal models of vascular remodeling. Methods and Results: The depletion of Girdin by RNA interference disrupted the rearrangement of the actin cytoskeleton in VSMCs, resulting in impaired cell migration. The depletion of Girdin also inhibited VSMC proliferation. Girdin expression was highly upregulated and its serine at position 1416 was phosphorylated in the neointima of carotid arteries after balloon injury in a rat model. The introduction of an adenovirus harboring short hairpin RNA against Girdin attenuated the proliferation of VSMCs and neointima formation without affecting reendothelialization. Furthermore, we found that neointima formation after femoral wire injury was significantly attenuated in Girdin S1416A knock-in mice, in which the Akt phosphorylation site of Girdin was mutated, thus indicating a major role for Girdin phosphorylation in vascular remodeling. Conclusions: These findings indicate that Girdin and its Akt-mediated phosphorylation have major roles in the migration and proliferation of VSMCs and vascular remodeling, making the Akt/Girdin signaling pathway a potential target for the development of new therapeutics for vascular diseases.
Intramural duodenal hematoma as a complication of pancreatic cancer
Authors: A.-L. Chou, K.-C. Tseng, Y.-H. Hsieh, W.-F. Feng, C.-A. Tseng
Journal: Endoscopy (2007)

Intramural duodenal hematoma (IDH) occurs mainly in children, secondarily to blunt abdominal injury. In adults, blunt abdominal trauma accounts for 70 % of IDH cases [1]. Nontraumatic causes of IDH in adults include coagulation disorders, duodenal biopsy, and endoscopic injection therapy for bleeding ulcers [2]. Very few cases of IDH of pancreatic origin have been reported [3] [4] [5]. We describe a case of IDH presenting as a complication of pancreatic cancer. This report highlights the need to consider a malignant process as a possible etiology of IDH.
Effect of Acceptance or Rejection on the Author's Evaluation of Peer Review of Medical Manuscripts
Authors: Joseph M. Garfunkel
Journal: JAMA (1990)

To determine whether authors of rejected manuscripts would evaluate the editorial review process less favorably than would authors of manuscripts accepted for publication, a questionnaire was sent to solicit evaluations of the quality of the reviews that had led to the rejection or acceptance of manuscripts submitted to the<i>Journal of Pediatrics</i>. Similar evaluations of the editor's letter were also sought. Authors were more likely to respond to the questionnaire if their manuscripts had been accepted and were more likely to complete the questionnaire thoroughly. Authors of accepted manuscripts evaluated the editor's communication more favorably than did the authors of manuscripts not accepted for publication, but the evaluations of the reviews were not significantly different. Most authors utilized the reviews to modify their manuscripts before submitting them to another journal. (<i>JAMA</i>. 1990;263:1376-1378)