tbuckley/cabot-search huggingface dataset:
HIV-1 envelope gp41 is a potent inhibitor of chemoattractant receptor expression and function in monocytes.
Authors: H Ueda, O M Howard, M C Grimm, S B Su, W Gong, G Evans, F W Ruscetti, J J Oppenheim, J M Wang
Journal: Journal of Clinical Investigation (1998)

HIV-1 uses CD4 and chemokine receptors as cofactors for cellular entry. The viral envelope transmembrane protein gp41 is thought to participate in viral fusion with CD4(+) cells. We investigated whether gp41 interacts with chemokine receptors on human monocytes by testing its effect on the capacity of cells to respond to chemokine stimulation. Monocytes preincubated with gp41 of the MN strain showed markedly reduced binding, calcium mobilization, and chemotaxis in response to a variety of chemokines as well as to the bacterial peptide fMLP. This generalized inhibition of monocyte activation by chemoattractants required the presence of CD4, since the effect of gp41 was only observed in CD4(+) monocytes and in HEK293 cells cotransfected with chemokine receptors and an intact CD4, but not a CD4 lacking its cytoplasmic domain. Confocal microscopy showed that gp41 caused internalization of CXCR4 in HEK293 cells provided they were also cotransfected with intact CD4. In addition, pretreatment of monocytes with protein kinase C inhibitors partially reversed the inhibitory effect of gp41. Thus, gp41, which had not previously been implicated as interacting with HIV-1 fusion cofactors, downregulates chemoattractant receptors on monocytes by a CD4-dependent pathway.
Unique microRNA molecular profiles in lung cancer diagnosis and prognosis
Authors: Nozomu Yanaihara, Natasha Caplen, Elise Bowman, Masahiro Seike, Kensuke Kumamoto, Ming Yi, Robert M. Stephens, Aikou Okamoto, Jun Yokota, Tadao Tanaka, George Adrian Calin, Chang-Gong Liu, Carlo M. Croce, Curtis C. Harris
Journal: Cancer Cell (2006)
Transgenic expression of hepatitis C virus structural proteins in the mouse
Authors: T Kawamura, A Furusaka, M J Koziel, R T Chung, T C Wang, E V Schmidt, T J Liang
Journal: Hepatology (1997)

Although hepatitis C virus (HCV) is a leading cause of morbidity and mortality worldwide, the role of viral cytopathic effects remains unclear. To study the biosynthesis of HCV structural proteins and their pathogenic role, we constructed transgenic mice, expressing type 1b HCV structural proteins (core, E1, and E2) in liver tissues. Two liver-specific promoters were used. The mouse major urinary protein (MUP) promoter has been shown to be developmentally regulated with little or no expression in utero but high-level expression after birth. The albumin (Alb) promoter provides constitutive, high levels of transgenes in live. Expression of both HCV transgenes was detected in several lines by Northern blots, HCV-specific reverse transcriptase-polymerase chain reactions (RT-PCR), and Western immunoblotting. Alb HCV lines showed higher levels of HCV expression than the MUP HCV lines. Immunohistochemical analysis revealed a predominantly cytoplasmic presence of core protein with occasional nuclear staining, and both cytoplasmic and membrane expression of the E2 protein in the transgenic livers. In both transgenes, the highest levels of both antigens were seen in perivenular hepatocytes, suggesting potential processing specificity in those cells. At six months of age, the livers of all transgenic lineages remained histologically normal. We concluded that HCV structural proteins are not directly cytopathic in this animal model.
Positive somatostatin receptor scintigraphy correlates with the presence of somatostatin receptor subtype 2.
Authors: M John, W Meyerhof, D Richter, B Waser, J C Schaer, H Scherubl, J Boese-Landgraf, P Neuhaus, C Ziske, K Molling, E O Riecken, J C Reubi, B Wiedenmann
Journal: Gut (1996)

Somatostatin receptor scintigraphy (SRS) is positive in approximately 75% of all patients with neuroendocrine gastroenteropancreatic tumours. This study aimed to identify specific somatostatin receptor (sstr) subtypes, which are responsible for the in vivo binding of the widely used somatostatin analogue, octreotide in human neuroendocrine gastroenteropancreatic tumours. Twelve patients underwent SRS with radiolabelled octreotide. After surgical resection, tumour tissues were analysed in vitro for somatostatin and octreotide binding sites by autoradiography. In addition, for the first time, sstr subtype mRNA expression was examined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Tumour tissues from all SRS positive patients were positive by autoradiography. Semiquantitative RT-PCR revealed most prominently sstr2 expression in scintigraphically positive tumours. Two SRS negative tumours contained in vitro octreotide binding sites as well as high levels of sstr1 and sstr2 mRNAs. Positive SRS is mainly due to sstr2. sstr1, 3, 4, and probably 5 are less important for in vivo octreotide binding. False negative scintigraphic results seem to be influenced by factors independent of the expression of specific sstr.
Usefulness of vessel-sealing devices combined with crush clamping method for hepatectomy: A retrospective cohort study
Authors: Atsushi Nanashima, Takafumi Abo, Junichi Arai, Katsunori Takagi, Hirofumi Matsumoto, Hiroaki Takeshita, Tomoshi Tsuchiya, Takeshi Nagayasu
Journal: International Journal of Surgery (2013)
Manganese-dependent NADPH oxidation by granulocyte particles. The role of superoxide and the nonphysiological nature of the manganese requirement.
Authors: J T Curnutte, M L Karnovsky, B M Babior
Journal: Journal of Clinical Investigation (1976)

Recent work has indicated that superoxide is involved in the manganese-stimulated oxidation of NADPH by crude granule preparations of guinea pig neutrophils. The characteristics of a model manganese-requiring NADPH-oxidizing system that employs a defined O2-generator have now been compared to the original neutrophil-granule system. With respect to pH dependence, cyanide sensitivity, and reduced pyridine nucleotide specificity, the properties of the two systems are very similar. Additional information has been obtained concerning cation specificity and the kinetics of the metal-catalyzed NADPH oxidation. From the similarities between the properties of the model and neutrophil particle systems, we postulate that the manganese-dependent NADPH oxidation observed in the presence of neutrophil granules represents in large part of nonenzymatic free radical chain involving the oxidation of NADPH to NADP, with O2- as both the chain initiator and one of the propagating species. In this reaction, the neutrophil particles serve only as a source of O2-. Further, the same changes in kinetics (decrease in apparent Km for NADPH) observed previously when granules from phagocytizing rather than resting cells were employed could be mimicked by varying the rate of O2-generation by the model system. We conclude from these results that it is unnecessary to invoke a manganese-requiring enzyme as a component of the phagocytically stimulated respiratory system of the neutrophil.
Photoaccentuated erythroderma associated with CD4+ T lymphocytopenia: Successful treatment with 5-methoxypsoralen and UVA, interferon alfa-2b, and extracorporeal photopheresis
Authors: Peter Wolf, Robert Müllegger, Lorenzo Cerroni, Reingard Aigner, Gerhard Fueger, Gerald Höfler, Johann Derbaschnig, Helmut Kerl
Journal: Journal of the American Academy of Dermatology (1996)
Efficacy of Heparin Loading During an 18F-FDG PET/CT Examination to Search for Cardiac Sarcoidosis Activity
Authors: Kimiteru Ito, Miyako Morooka, Osamu Okazaki, Ryogo Minaminoto, Kazuo Kubota, Michiaki Hiroe
Journal: Clinical Nuclear Medicine (2013)

A 65-year-old woman with a complete atrioventricular block was diagnosed as having cardiac sarcoidosis. (18)F-FDG PET/CT imaging without unfractionated heparin loading revealed systemic abnormal uptake indicating sarcoidosis. However, the cardiac lesions were vague because of the physiological FDG uptake. One month later, (18)F-FDG PET/CT using heparin loading was performed to evaluate the lesion activity prior to the start of steroid administration. (18)F-FDG PET/CT imaging with heparin loading showed the cardiac lesions more clearly and suppressed the FDG uptake in normal myocardium. Heparin loading during FDG PET/CT may be useful for detecting cardiac involvement in patients with cardiac sarcoidosis.
1063-63 Relationship of troponin I elevation after uncomplicated coronary stenting with thrombotic (D-dimer), inflammatory (C-reactive protein and fibrinogen), procedural, and clinical factors
Authors: Jose M De la Torre-Hernandez, Susana Gonzalez-Enriquez, Fermin Sainz-Laso, Jose M Cuesta, Alvaro Figueroa, Javier Zueco, Thierry Colman
Journal: Journal of the American College of Cardiology (2004)
Laboratory Infection with Louping-ill Virus: a Case Study
Authors: W. C. Cooper, I. J. Green, J. W. Fresh
Journal: BMJ (1964)

An explosive outbreak affecting 404 pupils and two members of staff at three Coventry secondary modern schools is described, in which the prominent symptoms were frontal headache, nausea, and vertigo, accompanied by actual collapse.Arguments are put forward for considering the outbreak to be of infectious (probably viral) origin, although it is admitted that hysterical elements were probably also present.An account is given of the attempted measures of control, drawing attention in particular to the part played by exclusion and finally by school closure.Mention is made of the practical difficulties involved in dealing with an outbreak of this type of "group illness" in a localized community.We should like to express our gratitude to Dr. J.
Intraluminal and intracavitary vacuum therapy for esophageal leakage: a new endoscopic minimally invasive approach
Authors: G. Loske, T. Schorsch, C. Müller
Journal: Endoscopy (2011)

Endoscopic treatment by placement of a vacuum sponge drainage system is a new option in the management of leakages in the digestive tract. We now distinguish between two treatment variants: the intracavitary and intraluminal techniques. A drainage system comprising an appropriately trimmed polyurethane foam sponge and a gastric-type tube is either placed through the esophageal defect into an extraluminal wound cavity (intracavitary method), or directly onto the defect with the sponge remaining within the esophageal lumen (intraluminal method). Continuous negative pressure of 125 mmHg is then applied, resulting in stabilizing of the sponge and continuous drainage and sealing of the defect. We report a case series of 14 patients, presenting the full range of possible esophageal defects that were successfully treated with either intracavitary or intraluminal vacuum therapy. Complete healing of the esophageal defect was achieved in 13 patients; one patient died due to fulminant pseudomembranous colitis while the esophageal defect was nearly healed.
(50) Eosinophilic cellulitis
Authors: T.J. O'Brien, M.W. Greaves
Journal: British Journal of Dermatology (1983)

Hairless rats fed a hypomagnesaemic diet developed an inflammatory dermatosis characterized by papular erythematous plaques. The dermatosis was long-lasting and could be observed for up to 6 months. It was inhibited by intraperitoneal injection of magnesium or dexamethasone but not by mepyramine, cimetidine, theophylline, aspirin or indomethacin. Analysis of semithin sections only showed oedema in the epidermis and superficial dermis with occasional intra-epidermal splitting. Direct immunofluorescence did not detect immunoreactant deposits within epidermis or dermis. Hypomagnesaemic dermatosis in hairless rats is proposed as a model for the pharmacological study of skin inflammation.
In Vivo Function of an Interleukin 2 Receptor β Chain (IL-2Rβ)/IL-4Rα Cytokine Receptor Chimera Potentiates Allergic Airway Disease
Authors: Jeehee Youn, Jin Chen, Shreevrat Goenka, Mark A. Aronica, Ana L. Mora, Victor Correa, James R. Sheller, Mark Boothby
Journal: The Journal of Experimental Medicine (1998)

Strength of T cell receptor (TCR) signaling, coreceptors, costimulation, antigen-presenting cell type, and cytokines all play crucial roles in determining the efficiency with which type 2 T lymphocytes (Th2, Tc2) develop from uncommitted precursors. To investigate in vivo regulatory mechanisms that control the population of type 2 T cells and disease susceptibility, we have created lines of transgenic mice in which expression of a chimeric cytokine receptor (the mouse interleukin 2 receptor β chain [IL-2Rβ] extracellular domain fused to the cytoplasmic tail of IL-4Rα) is targeted to the T lymphoid lineage using the proximal lck promoter. This chimera transduced IL-4–specific signals in response to IL-2 binding and dramatically enhanced type 2 responses (IL-4, IL-5, and immunoglobulin E production) upon in vitro TCR stimulation or in vivo antigen challenge. Thus, type 2 effector function was augmented by IL-4 signals transduced through a chimeric receptor expressed in a T cell–specific manner. This influence was sufficient for establishment of antigen-induced allergic airway hyperresponsiveness on a disease-resistant background (C57BL/6).
Outbreak of Streptococcal Wound Infections
Authors: Pedro A. Poma
Journal: JAMA (1983)

<h3>To the Editor.—</h3> Berkelman et al, in their article entitled "Streptococcal Wound Infections Caused by a Vaginal Carrier" (1982;247:2680), present an elegant piece of successful investigative work. As I assume nurse A, the carrier, agreed voluntarily to all that testing and treatment she received, should not other members of her household, including her sexual partner, have been examined and treated if required? If she was contagious at work, would not she be contagious at home? And, if a surgeon was found to be the carrier, would the hospital medical staff temporarily suspend this person's patient-care duties? Are physicians legally required to submit to this testing?
Managers will have more say in merit awards
Authors: L Beecham
Journal: BMJ (1994)

NHS employers will have a greater say in the allocation of distinction awards, and information about who has an award will be more easily accessible. But a government working party has decided against recommending the replacement of the current system by “some other less well tried form of performance related pay.”

The working party was chaired by the Scottish chief medical officer, Dr Robert Kendell, and included representatives of the BMA, the royal colleges, and NHS chairpeople and managers. It was set up in November last year to recommend a new scheme for rewarding performance, taking account of the NHS reforms. This followed criticism that the system was too secretive and was based on a system of peer review.

Some changes have already taken place. A …
Letter: "Lost threads" with intrauterine devices.
Authors: J Guilleband, J Kasonde
Journal: BMJ (1974)

parent.In your leading article (17 August, p. 430) you express an opinion that was discarded by most ophthalmologists in Bri- tain many years ago.Your support for this del-ayed surgery is lperpetuating an idea which results in many children not developing any form of binocular vision and is per- forming a grave disservice to squinting
Is Glucose Control Important for Prevention of Cardiovascular Disease in Diabetes?
Authors: Edoardo Mannucci, Ilaria Dicembrini, Angelo Lauria, Paolo Pozzilli
Journal: Diabetes Care (2013)

Patients affected by diabetes show an increased risk of cardiovascular disease (CVD) and mortality that reduces their life expectancy by 5–15 years (depending on the age at diagnosis). An 18-year follow-up study from Finland demonstrated a similar impact of type 1 and type 2 diabetes on cardiovascular mortality, with an increased risk of 5.2 and 4.9 times for type 1 and type 2 diabetes, respectively (1). In type 1 diabetes, follow-up results from a large randomized clinical trial suggest that the improvement of metabolic control, obtained through intensive insulin treatment, can prevent CVD in the long term. On the other hand, despite some encouraging results (2,3), the results of trials assessing the long-term cardiovascular effects of improving metabolic control in type 2 diabetes are controversial. Here, we will present the main points supporting and will illustrate the main counterpoints challenging the importance of glucose control for prevention of CVD in diabetic patients.

### Pros

#### Pathophysiological effects of hyperglycemia on cardiovascular system.

There is convincing evidence from epidemiological and pathophysiological studies that hyperglycemia has a detrimental effect on cardiovascular risk profile in its own right. It is well known that among patients with type 2 diabetes, those with higher levels of blood glucose and HbA1c are at greater risk for CVD. Glycemic fluctuations and chronic hyperglycemia are triggers for inflammatory responses via increased endoplasmic reticulum stress and mitochondrial superoxide production. The molecular pathways underlying hyperglycemia, low-grade inflammation, and oxidative stress have been widely recognized in the pathogenesis of endothelial dysfunction, which represents the first step of atherogenesis. Through this pathway, hyperglycemia-induced early atherogenesis may lead to an increased probability of cardiovascular events later in life. Direct effects of glucose toxicity, oxidative stress, and low-grade inflammation act in a vicious cycle that determines impaired insulin sensitivity, β-cell loss, and endothelial dysfunction, thus leading to micro- and macrovascular complications …
Graham Cleverly Pritchard
Authors: B. Pritchard
Journal: BMJ (2010)

Graham Pritchard died on Tuesday 23 March 2010 at the age of 96.

Graham followed his father, a general practitioner in Highgate, into medicine. He studied at Clare College, Cambridge, and King’s College Hospital, London, where he met and in April 1943 married a nurse, Rosemary Newton. At the outbreak of the second world war he had joined the Royal Army Medical Corps and …
What's the point?
Authors: T. Groves
Journal: BMJ (2011)

In Anke Steckelberg and colleagues’ randomised controlled trial in Germany, comparing the effect of evidence based information about screening for colorectal cancer with that of standard information, the primary outcome was “informed choice” among nearly 1500 people eligible for screening (doi:10.1136/bmj.d3193). This outcome, adapted from a validated instrument and assessed by questionnaires, was a composite of knowledge + attitude + uptake of screening (actual and planned uptake). Unsurprisingly, more participants in the intervention group made an informed choice (44% v 12.8% in the control group, 99% confidence interval 25.7% to 36.7%; P<0.001). But, counterintuitively, the …
AN INHIBITOR OF THE NLRP3 INFLAMMASOME 16673-34-0 REDUCES INFARCT SIZE IN A MOUSE MODEL OF MYOCARDIAL ISCHEMIA REPERFUSION INJURY
Authors: Carlo Marchetti, Stefano Toldo, Jeremy Chojnacki, Eleonora Mezzaroma, Massimo Federici, Norbert F. Voelkel, Benjamin W. Van Tassell, Shijun Zhang, Antonio Abbate
Journal: Journal of the American College of Cardiology (2014)
The Responses of Rat Intestinal Brush Border and Cytosol Peptide Hydrolase Activities to Variation in Dietary Protein Content DIETARY REGULATION OF INTESTINAL PEPTIDE HYDROLASES
Authors: J. Alex Nicholson, Denis M. McCarthy, Young S. Kim
Journal: Journal of Clinical Investigation (1974)

The effects of variation in dietary protein content on small intestinal brush border and cytosol peptide hydrolase activities have been investigated. One group of rats was fed a high protein diet (55% casein) and another group was fed a low protein diet (10% casein). After 1 wk, brush border peptide hydrolase activity (L-leucyl-beta-naphthylamide as substrate) and cytosol peptide hydrolase activity (L-prolyl-L-leucine as substrate) were determined in mucosae taken from the proximal, middle, and distal small intestine. As judged by several parameters, brush border peptide hydrolase activity was significantly greater in rats fed the high protein diet when data for corresponding segments were compared. In contrast, no significant difference was seen in cytosol peptide hydrolase activity. IN A SECOND STUDY, BRUSH BORDER AND CYTOSOL PEPTIDE HYDROLASE ACTIVITIES WERE DETERMINED IN THE PROXIMAL INTESTINE BY UTILIZING AN ADDITIONAL THREE PEPTIDE SUBSTRATES: L-leucyl-L-alanine, L-phenylalanylglycine, and glycyl-L-phenylalanine. Sucrase, maltase, and alkaline phosphatase activities were also determined. As before, brush border peptide hydrolase activities were significantly greater in rats fed the high protein diet. However, activities of the nonproteolytic brush border enzymes did not vary significantly with diet. In contrast to the results obtained with L-prolyl-L-leucine as substrate for the cytosol enzymes, cytosol activity against the three additional peptide substrates was greater in rats fed the high protein diet. It is suggested that the brush border peptide hydrolase response to variation in dietary protein content represents a functional adaptation analogous to the regulation of intestinal disaccharidases by dietary carbohydrates. The implication of the differential responses of the cytosol peptide hydrolases is uncertain, since little is known of the functional role of these nonorgan-specific enzymes.
Right atrial size and deformation in patients with dilated cardiomyopathy undergoing cardiac resynchronization therapy
Authors: Antonello D'Andrea, Raffaella Scarafile, Lucia Riegler, Gemma Salerno, Rita Gravino, Rosangela Cocchia, Francesca Castaldo, Filomena Allocca, Giuseppe Limongelli, Giovanni Di Salvo, Sergio Cuomo, Giuseppe Pacileo, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò
Journal: European Journal of Heart Failure (2009)
HLA-DRB1*04 is a novel fetal susceptibility allele in congenital heart block
Authors: T. Ostberg, S. Gorgen, S. Salomonsson, B. Ding, H. Eliasson, A. Elfving, A. Malarstig, L. Alfredsson, L. Klareskog, A. Hamsten, T. Olsson, L. Padukov, T. Axelsson, F. Gadler, A. Jonzon, S. E. Sonesson, I. Kockum, M. Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> Congenital heart block may develop in the fetus of Ro52 autoantibody positive women. The reported recurrence rate for autoantibody associated congenital heart block is however only 10–25%, indicating that other factors than maternal autoantibodies influence the disease development and fetal outcome. The most potent genetic influence on susceptibility to autoimmune diseases is the human leucocyte antigen (HLA) locus, and as there is a strong and well-known HLA-DR*03 allele association with systemic lupus erythematosus, Sjögren9s syndrome and production of Ro/SSA autoantibodies, the authors hypothesised that specific alleles of the HLA locus may render the fetus susceptible to congenital heart block induced by maternal autoantibodies. <h3>Methods</h3> Genotyping was performed for 561 490 single-nucleotide polymorphisms (SNPs) in DNA from Swedish Caucasian families with a Ro/SSA autoantibody positive mother and with at least one case of congenital heart block. Full HLA-A, HLA-C and HLA-DRB1 allele typing was performed by single specific primer PCR in 60 families with complete trios. Swedish Caucasian population-based healthy controls were used in case-control association analysis. Genetic linkage was analysed by transmission disequilibrium test. <h3>Results</h3> A case-control analysis between the index cases and population-based controls revealed an association of congenital heart block with six SNPs in the 6p21 major histocompatibility complex (MHC) locus at a genome-wide significance of p&lt;5×10<sup>−8</sup> (OR 2.57–3.12). In family-based association analysis of distinct MHC class I and II alleles the authors observed an association of the HLA-DR*04 (p=0.01), DR*13 (p=0.02) and Cw6 (p=0.03) alleles with congenital heart block. HLA-DR*04 was significantly more often transmitted to children who developed congenital heart block, while the opposite was true for HLA-DR*13 and Cw6. <h3>Conclusions</h3> This study identifies HLA-DRB1*04 as a novel fetal genetic variant that confers susceptibility to develop congenital heart block in response to exposure to Ro/SSA autoantibodies, while HLA-DR*13 and Cw6 provide resistance.