tbuckley/cabot-search huggingface dataset:
Mechanism of resistance to complement-mediated killing of bacteria encoded by the Salmonella typhimurium virulence plasmid gene rck.
Authors: E J Heffernan, S Reed, J Hackett, J Fierer, C Roudier, D Guiney
Journal: Journal of Clinical Investigation (1992)

We find that pADEO16, a recombinant cosmid carrying the rck gene of the Salmonella typhimurium virulence plasmid, when cloned into either rough or smooth Escherichia coli and Salmonella strains, confers high level resistance to the bactericidal activity of pooled normal human serum. The rck gene encodes a 17-kD outer membrane protein that is homologous to a family of virulence-associated outer membrane proteins, including pagC and Ail. Complement depletion, C3 and C5 binding, and membrane-bound C3 cleavage products are similar in strains with and without rck. Although a large difference in C9 binding was not seen, trypsin cleaved 55.7% of bound 125I-C9 counts from rough S. typhimurium with pADEO16, whereas only 26.4% were released from S. typhimurium with K2011, containing a mutation in rck. The majority of C9 extracted from rck strain membranes sediments at a lower molecular weight than in strains without rck, suggesting less C9 polymerization. Furthermore, SDS-PAGE analysis of gradient peak fractions indicated that the slower sedimenting C9-containing complexes in rck strains did not contain polymerized C9 typical of the tubular membrane attack complex. These results indicate that complement resistance mediated by Rck is associated with a failure to form fully polymerized tubular membrane attack complexes.
Studies in primary hypomagnesaemia: evidence for defective carrier-mediated small intestinal transport of magnesium.
Authors: P J Milla, P J Aggett, O H Wolff, J T Harries
Journal: Gut (1979)

A 4 year old male with primary hypomagnesaemia was studied using balance and steady-state perfusion techniques. Magnesium balance was negative and could be accounted for by increased faecal losses, renal conservation being normal; calcium balance was normal. After oral magnesium therapy magnesium balance became positive. The perfusion studies demonstrated net loss of magnesium into the intestinal lumen when low concentrations (1 and 2 mmol/l) of magnesium were perfused in contrast with control subjects; whereas at high concentrations (10 mmol/l a net absorption of a magnitude similar to control values was observed. In the control subjects sequential perfusion of increasing concentrations of magnesium demonstrated a curvilinear relationship between rates of absorption and the lower concentrations (1, 2, and 4 mmol/l) with an apparent Km and Vmax of 4.5 mmol/l and 91 nmol/min/cm respectively. At the higher concentrations (6 and 10 mmol/l) the relationship was linear. These data suggest that two separate transport systems participate in the absorption of magnesium from the proximal small intestine; a carrier-mediated system which saturates at low intraluminal concentrations, and a simple diffusional process. The possibility of the second transport system being a carrier-mediated process with a very much higher Km cannot be excluded. In primary hypomagnaesaemia the results suggest that the primary abnormality is a defect in carrier-mediated transport of magnesium from low intraluminal concentrations of magnesium.
Framework for design and evaluation of complex interventions to improve health
Authors: M. Campbell
Journal: BMJ (2000)

Randomised controlled trials are widely accepted as the most reliable method of determining effectiveness, but most trials have evaluated the effects of a single intervention such as a drug. Recognition is increasing that other, non-pharmacological interventions should also be rigorously evaluated.1-3 This paper examines the design and execution of research required to address the additional problems resulting from evaluation of complex interventions—that is, those “made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper (www.mrc.ac.uk/complex_packages.html). We focus on randomised trials but believe that this approach could be adapted to other designs when they are more appropriate.

#### Summary points

Complex interventions are those that include several components

The evaluation of complex interventions is difficult because of problems of developing, identifying, documenting, and reproducing the intervention

A phased approach to the development and evaluation of complex interventions is proposed to help researchers define clearly where they are in the research process

Evaluation of complex interventions requires use of qualitative and quantitative evidence

There are specific difficulties in defining, developing, documenting, and reproducing complex interventions that are subject to more variation than a drug. A typical example would be the design of a trial to evaluate the benefits of specialist stroke units. Such a trial would have to consider the expertise of various health professionals as well as investigations, drugs, treatment guidelines, and arrangements for discharge and follow up. Stroke units may also vary in terms of organisation, management, and skill mix. The active components of the stroke unit may be difficult to specify, making it difficult to replicate the intervention. The box gives other examples of complex interventions.

#### Examples of complex interventions

Service delivery and organisation:

Stroke units

Hospital at home

Interventions directed at health professionals' behaviour:

Strategies for implementing guidelines

Computerised decision support

Community interventions:

Community …
Suppression of Tumorigenicity in Breast Cancer Cells by the Microfilament Protein Profilin 1
Authors: Jürgen Janke, Kathrin Schlüter, Burkhard Jandrig, Michael Theile, Konrad Kölble, Wolfgang Arnold, Edgar Grinstein, Arnfried Schwartz, Lope Estevéz-Schwarz, Peter M. Schlag, Brigitte M. Jockusch, Siegfried Scherneck
Journal: The Journal of Experimental Medicine (2000)

Differential display screening was used to reveal differential gene expression between the tumorigenic breast cancer cell line CAL51 and nontumorigenic microcell hybrids obtained after transfer of human chromosome 17 into CAL51. The human profilin 1 (PFN1) gene was found overexpressed in the microcell hybrid clones compared with the parental line, which displayed a low profilin 1 level. A comparison between several different tumorigenic breast cancer cell lines with nontumorigenic lines showed consistently lower profilin 1 levels in the tumor cells. Transfection of PFN1 cDNA into CAL51 cells raised the profilin 1 level, had a prominent effect on cell growth, cytoskeletal organization and spreading, and suppressed tumorigenicity of the stable, PFN1-overexpressing cell clones in nude mice. Immunohistochemical analysis revealed intermediate and low levels of profilin 1 in different human breast cancers. These results suggest profilin 1 as a suppressor of the tumorigenic phenotype of breast cancer cells.
Revisiting an old acquaintance: role for eIF5A in diabetes
Authors: Joachim Hauber
Journal: Journal of Clinical Investigation (2010)

Dysfunction of pancreatic islet beta cells underlies both type 1 and type 2 diabetes and appears to result in part from the local release of proinflammatory cytokines. An improved understanding of the mechanisms that mediate islet responsiveness to proinflammatory cytokines may therefore expand our knowledge of the role of cytokine signaling in the development of diabetes, providing potential new targets for the development of therapeutics to protect pancreatic islets from inflammation. In this issue of the JCI, Maier and colleagues identify eukaryotic translation initiation factor 5A (eIF5A) as a critical regulator of the inflammatory response in mouse pancreatic islets. I believe these data provide new and important insights into the regulatory pathways that contribute to the development of diabetes and deepen our understanding of the function of the, so far, rather enigmatic cellular protein eIF5A.
Cardiac alternans: mechanisms and pathophysiological significance
Authors: D Euler
Journal: Cardiovascular Research (1999)

Time for primary review 31 days. 

Mechanical alternans (pulsus alternans) is a condition in which there is a beat-to-beat oscillation in the strength of cardiac muscle contraction at a constant heart rate. Since the first description of pulsus alternans by Traube in 1872 [1], there has been continuing interest in understanding the mechanisms and clinical manifestations of this phenomenon [2,3]. Initially observed in the hearts of laboratory animals, the phenomenon has been reported frequently in patients particularly those with severe heart failure and aortic valve disease. Although much is known about the cellular mechanisms of alternans in isolated cardiac muscle preparations, little is known about the mechanisms by which changes in preload or afterload evoke alternans in the intact heart. The purpose of this review article is to discuss the mechanisms of alternans at both the cellular level and in the intact heart. The relationship between mechanical and electrical alternans is reviewed. The role of sympathetic nervous system is discussed as a means of protecting the heart from alternans during accelerations of heart rate. Since pulsus alternans has been reported in patients with cardiac disease, the diagnostic and prognostic significance of mechanical and electrical alternans is also discussed.

The ability to induce mechanical alternans by rapid driving frequencies appears to be a fundamental property of mammalian ventricular muscle. Experimental studies have shown that by varying the pacing cycle length over a wide range, it is possible to define a critical cycle length (threshold) for the induction of sustained mechanical alternans [4–7]. Driving the heart at cycle lengths shorter than the threshold cycle length may increase the amplitude of the beat-to-beat oscillations in contraction strength (Fig. 1). Driving the heart at cycle lengths just longer than the threshold may produce transient alternans [4,6]. Transient alternans may also … 

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Idiopathic thrombocytopenic purpura in hodgkin's disease after splenectomy
Authors: Antonio Julia, Sherwood P. Miller
Journal: American Journal of Hematology (1976)

Abstract This is a report of a patient with Hodgkin's disease who underwent a staging splenectomy and extensive radiation therapy and then developed “idiopathic” thrombocytopenic purpura. This appears to be the second known instance of such a combination of events. The patient was in complete remission of his Hodgkin's disease from radiation therapy at the time and continues in remission 56 mo since completing therapy. There was a complete and, apparently, permanent response of the thrombocytopenic purpura to a course of corticosteroid therapy.
Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death.
Authors: H W Harris, C Grunfeld, K R Feingold, T E Read, J P Kane, A L Jones, E B Eichbaum, G F Bland, J H Rapp
Journal: Journal of Clinical Investigation (1993)

The hypertriglyceridemia of infection was traditionally thought to represent the mobilization of substrate to fuel the body's response to the infectious challenge. However, we have previously shown that triglyceride-rich lipoproteins can protect against endotoxin-induced lethality. The current studies examine the mechanism by which this protection occurs. Rats infused with a lethal dose of endotoxin preincubated with chylomicrons had a reduced mortality compared with rats infused with endotoxin alone (15 vs. 76%, P < 0.001). Preincubation with chylomicrons increased the rate of clearance of endotoxin from plasma and doubled the amount of endotoxin cleared by the liver (30 +/- 1 vs. 14 +/- 2% of the total infused radiolabel, P < 0.001). In addition, autoradiographic studies showed that chylomicrons directed more of the endotoxin to hepatocytes and away from hepatic macrophages. Rats infused with endotoxin plus chylomicrons also showed reduced peak serum levels of tumor necrosis factor as compared with controls (14.2 +/- 3.3 vs. 44.9 +/- 9.5 ng/ml, mean +/- SEM, P = 0.014). In separate experiments, chylomicrons (1,000 mg triglyceride/kg) or saline were infused 10 min before the infusion of endotoxin. Chylomicron pretreatment resulted in a reduced mortality compared with rats infused with endotoxin alone (22 vs. 78%, P < 0.005). Therefore, chylomicrons can protect against endotoxin-induced lethality with and without preincubation with endotoxin. The mechanism by which chylomicrons protect against endotoxin appears to involve the shunting of endotoxin to hepatocytes and away from macrophages, thereby decreasing macrophage activation and the secretion of cytokines.
Tissue microarray-based study of patients with lymph node-negative breast cancer shows that HER2/neu overexpression is an important predictive marker of poor prognosis
Authors: Y.H. Choi, J.H. Ahn, S.-B. Kim, K.-H. Jung, G.-Y. Gong, M.-J. Kim, B.-H. Son, S.-H. Ahn, W.K. Kim
Journal: Annals of Oncology (2009)
Hypocapnia and increased ventilatory responsiveness in patients with idiopathic central sleep apnea.
Authors: A Xie, R Rutherford, F Rankin, B Wong, T D Bradley
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We previously demonstrated that central apneas during sleep in patients with idiopathic central sleep apnea (ICSA) are triggered by abrupt hyperventilation. In addition, baseline PCO2 at the time of augmented breaths which triggered central apneas was lower than for augmented breaths which did not trigger apneas. These observations led us to hypothesize that patients with ICSA chronically hyperventilate maintaining their PCO2 close to the threshold for apnea during sleep owing to increased chemical respiratory drive. To test these hypotheses, we recorded transcutaneous PCO2 (PtcCO2) during overnight sleep studies on nine consecutive patients with ICSA and nine sex-, age-, and body-mass-index-matched control subjects. Daytime PaCO2 as well as rebreathing and single breath ventilatory responses to CO2 were also measured. Compared with the control subjects, the patients had significantly lower mean PtcCO2 during sleep (37.8 +/- 1.2 versus 42.7 +/- 10.9 mm Hg, p < 0.01) and lower PaCO2 while awake (35.1 +/- 1.3 versus 38.8 +/- 0.9 mm Hg, p < 0.05). Furthermore, patients with ICSA had significantly higher ventilatory responses to CO2 for both the rebreathing (3.14 +/- 0.34 versus 1.60 +/- 0.32 L/min/mm Hg, p < 0.005) and single breath methods (0.51 +/- 0.10 versus 0.25 +/- 0.04 L/min/mm Hg, p < 0.05). We conclude that: (1) patients with ICSA chronically hyperventilate awake and asleep and (2) chronic hyperventilation is probably related to augmented central and peripheral respiratory drive which predisposes to respiratory control system instability.
Paclitaxel and gemcitabine vs. paclitaxel and pegylated liposomal doxorubicin in advanced non–nasopharyngeal head and neck cancer. An efficacy and cost analysis randomized study conducted by the Hellenic Cooperative Oncology Group
Authors: G. Fountzilas, P. Papakostas, U. Dafni, T. Makatsoris, M. Karina, A. Kalogera-Fountzila, N. Maniadakis, G. Aravantinos, K. Syrigos, A. Bamias, C. Christodoulou, T. Economopoulos, H.P. Kalofonos, A. Nikolaou, N. Angouridakis, G. Stathopoulos, D. Bafaloukos, N. Pavlidis, J. Daniilidis
Journal: Annals of Oncology (2006)
Genomics and infectious disease: a call to identify the ethical, legal and social implications for public health and clinical practice
Authors: Gail Geller, Rachel Dvoskin, Chloe L Thio, Priya Duggal, Michelle H Lewis, Theodore C Bailey, Andrea Sutherland, Daniel A Salmon, Jeffrey P Kahn
Journal: Genome Medicine (2014)

Advances in genomics are contributing to the development of more effective, personalized approaches to the prevention and treatment of infectious diseases. Genetic sequencing technologies are furthering our understanding of how human and pathogen genomic factors - and their interactions - contribute to individual differences in immunologic responses to vaccines, infections and drug therapies. Such understanding will influence future policies and procedures for infectious disease management. With the potential for tailored interventions for particular individuals, populations or subpopulations, ethical, legal and social implications (ELSIs) may arise for public health and clinical practice. Potential considerations include balancing health-related benefits and harms between individuals and the larger community, minimizing threats to individual privacy and autonomy, and ensuring just distribution of scarce resources. In this Opinion, we consider the potential application of pathogen and host genomic information to particular viral infections that have large-scale public health consequences but differ in ELSI-relevant characteristics such as ease of transmission, chronicity, severity, preventability and treatability. We argue for the importance of anticipating these ELSI issues in advance of new scientific discoveries, and call for the development of strategies for identifying and exploring ethical questions that should be considered as clinical, public health and policy decisions are made.
<i>Thorax</i>: the prostate years
Authors: Ian D Pavord, Andrew Bush
Journal: Thorax (2013)

Thorax had a good 2013. We were all buoyed by a large rise in our impact factor from 6.525 to 8.376, by far the largest rise seen in our specialty area, cementing our position as the second-ranked respiratory journal behind the American Journal of Respiratory and Critical Care Medicine (impact factor 11.041). We suspect this has led to an increase in submission of high-quality manuscripts and are hopeful that gains in impact factor will increase. In part our improved impact factor reflects a reduction in original articles published per edition from 10–12 to 8–10 with the introduction of new content published in the ‘Chest Clinic’ section aimed at the jobbing clinician without a major research interest. However, the tremendous hard work of the associate editors, deputy editors, reviewers and the editorial team and the high-quality manuscripts sent in by you, our readers, have been much more important and hugely appreciated factors.

The acceptance rate for original articles is now 11% and the overall acceptance rate is 23%. Editorial turnaround times continue to improve. The average time to first decision in 2013 was 19 days for all papers and the average time to first decision for reviewed papers was 40 days, a modest improvement from 2012. The instant reject rate has reduced from 43% to 37%. We have seen an increase in time from on-line publication to paper publication …
(21) Benign Hyperglobulinaemic Purpura
Authors: R.C.D. Staughton, G.C. Wells
Journal: British Journal of Dermatology (1974)

Journal Article (21) Benign Hyperglobulinaemic Purpura Get access R.C.D. Staughton, R.C.D. Staughton St Thomas’Hospital, London Search for other works by this author on: Oxford Academic Google Scholar G.C. Wells G.C. Wells St Thomas’Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue s10, 1 July 1974, Pages 66–68, https://doi.org/10.1111/j.1365-2133.1974.tb12523.x Published: 01 July 1974
THE ANTIGENIC RELATIONSHIP BETWEEN PROTEUS X-19 AND TYPHUS RICKETTSIA
Authors: M. Ruiz Castaneda
Journal: The Journal of Experimental Medicine (1934)

A soluble specific substance was isolated from Mexican typhus Rickettsia which gave, with Proteus X-19 antiserum and typhus human serum, the same precipitation reactions as the polysaccharides extracted from B. proteus OX-19. The soluble specific substance extracted from Rickettsia and Proteus OX-19 is likely to be of a polysaccharide nature owing to the strong Molisch reactions obtained with such extracts, the heat stability and the negative protein reactions (biuret). Since, however, it still contains 7 per cent nitrogen, this is not certain. In the antigenic composition of both Proteus X-19 and typhus Rickettsia there is a common soluble specific factor which is responsible for the Weil-Felix reaction.
Immunoglobulin Gene Transcription
Authors: L M Staudt, M J Lenardo
Journal: Annual Review of Immunology (1991)

Transcriptional regulation of the immunoglobulin (Ig) genes is one of the best-studied systems for understanding tissue-restricted gene control. Dissection of the Ig genes reveals that each contains multiple regulatory elements that are preferentially active in B lymphocytes. These include a promoter and one or more enhancer elements. Biochemical analysis and cloning of the genes for transactivator proteins has uncovered a variety of distinct proteins that are often members of gene families. The transactivators themselves are under complex regulation at the transcriptional level as well as by interactions with other proteins in the cell. It appears that the coordinate action of a select constellation of these transactivators conveys the information for tissue-specific expression of the Ig genes.
Unique Mammalian tRNA-Derived Repetitive Elements in Dermopterans: The t-SINE Family and Its Retrotransposition Through Multiple Sources
Authors: O. Piskurek
Journal: Molecular Biology and Evolution (2003)

Short interspersed nuclear elements (SINEs) are dispersed repetitive DNA sequences that are major components of all mammalian genomes. They have been described in almost all lineages of Euarchontoglires (rodents, rabbits, primates, flying lemurs, and tree shrews), except in flying lemurs. Most SINE family members are composed of three distinct regions: a 5′ tRNA-related region, a tRNA-unrelated region, and a short tandem repeat at the 3′ end that is AT-rich. The newly discovered SINE family in Cynocephalus deviates from this common structure. All 30 SINE loci analyzed in this family lack a tRNA-unrelated region and are composed exclusively of tRNA-related elements. Therefore, this novel SINE structure, described for the first time in mammalian genomes, was designated as t-SINE. The t-SINE family exhibits a high copy number and is specific to flying lemurs. Three major t-SINE subfamilies could be distinguished on the basis of characteristic nucleotides, deletions, insertions, and duplications. These sequence-specific characteristics within subfamilies and sub-subfamilies reveal that they are derived copies of distinct progenitors. We present evolutionary relationships between subfamilies and compare relationships between the subfamilies and the isoleucine tRNA gene. t-SINE amplification occurred through multiple sources and is supposedly mobilized via the L1-encoded reverse transcriptase-dependent retrotranspositional mechanism in trans.