tbuckley/cabot-search huggingface dataset:
The Evolutionary Rate of a Protein Is Influenced by Features of the Interacting Partners
Authors: T. Makino
Journal: Molecular Biology and Evolution (2006)

Rates of protein evolution are thought to be influenced by features of protein-protein interaction (PPI). However, the most important features of interaction for determining the evolutionary rate are poorly understood. Here, we consider four categories for PPIs in Saccharomyces cerevisiae. Properties we consider are the extent to which proteins interact with proteins of the same function or different function (DF) and the extent to which these interactions involve connections in the dense part or sparse part (SP) of a PPI network. Our findings are that proteins with DF-SP interactions evolve at the slowest rate of all the proteins examined.
Cyclophilin D, a Component of the Permeability Transition-Pore, Is an Apoptosis Repressor
Authors: Alexis Schubert, Stefan Grimm
Journal: Cancer Research (2004)

Abstract The permeability transition (PT)-pore is an important proapoptotic protein complex in mitochondria. Although it is activated by many signals for apoptosis induction, the role of its various subunits in cell death induction has remained largely unknown. We found that of its components, only the voltage-dependent anion channel in the outer mitochondrial membrane and the adenine nucleotide translocator-1 (ANT-1), a PT-pore subunit of the inner membrane, are apoptosis inducers. We also report that ANT-1’s direct interactor, cyclophilin D, can specifically repress ANT-1-induced apoptosis. In addition, cotransfection experiments revealed that for a diverse range of apoptosis inducers, cyclophilin D shows the same repression profile as the compound bongkrekic acid, a specific inhibitor of the PT-pore. This activity seems to be independent of its chaperone activity, the only known function of cyclophilin D to date. Importantly, cyclophilin D is specifically up-regulated in human tumors of the breast, ovary, and uterus, suggesting that inhibition of the PT-pore via up-regulation of cyclophilin D plays a role in tumorigenesis.
Gastric mucosal contraction and vascular injury induced by indomethacin precede neutrophil infiltration in the rat.
Authors: A Anthony, R Sim, A P Dhillon, R E Pounder, A J Wakefield
Journal: Gut (1996)

BACKGROUND: In contrast with earlier reports that neutrophils play a primary part in non-steroidal anti-inflammatory drug (NSAID) injury to the stomach, recent evidence suggests only a secondary role for these cells. AIM: To examine whether early microscopic changes induced by indomethacin in the gastric corpus of fasted rats and the antrum of fasted-refed rats involve neutrophil infiltration. METHODS: Oral indomethacin 30 mg/kg or vehicle was given to six groups of fasted rats that were killed five, 15, and 30 minutes after dosing. Subcutaneous indomethacin 30 mg/kg was also given to six groups of fasted-refed rats that were killed one, two, and four hours later. Haematoxylin and eosin and reticulin stained sections were examined to identify mucosal architectural changes. The gastric mucosa was also examined immunohistochemically for actin, fibrin, and neutrophils. RESULTS: In both the corpus and antrum, indomethacin caused an early phase of mucosal injury that occurred prior to mucosal neutrophil infiltration. Within the superficial corpus mucosa, this phase preceded coagulative necrosis and included surface epithelial expulsion, mucosal contraction with capillary aggregation and distortion, intravascular vascular fibrin deposition, and capillary congestion. The antrum showed similar early changes except that full thickness mucosal coagulative necrosis was a predominant early finding. CONCLUSIONS: In two experimental models of NSAID gastric ulceration the mucosa undergoes early contraction, vascular fibrin deposition, and necrosis prior to neutrophil infiltration. These findings support a primary, neutrophil independent, ischaemic pathogenesis for NSAID gastric ulceration.
Myb proteins inhibit fibroblast transformation by v-Rel
Authors: Shu-ling Fu, Brigitte Ganter, Joseph S Lipsick
Journal: Molecular Cancer (2006)

Abstract Genes that cause cancer have been divided into two general classes – oncogenes that act in a dominant fashion to transform normal cells into a malignant state, and tumor suppressor genes that act in a dominant fashion to prevent such transformation. In this report, we demonstrate that both the v- myb retroviral oncogene, which causes leukemic transformation of hematopoietic cells, and the c- myb proto-oncogene can also function as inhibitors of fibroblast transformation by the v- rel oncogene. These results imply that the myb genes can function either as oncogenes or as tumor suppressors in different cellular contexts.
Doctors and quality improvement
Authors: Peter M Hockey, Martin N Marshall
Journal: Journal of the Royal Society of Medicine (2009)

Doctors are trained to diagnose and treat ill health. Within the confines of the one‐to‐one relationship with patients behind the closed door of the consulting room most clinicians fulfil this role highly successfully. But the traditional role of the doctor is carried out within a broader historical, organizational, social and political context – where the diagnosis and treatment of system failures can be as important as clinical interactions with individual patients. Unless doctors are willing to understand and influence this wider context, their ability to improve health outcomes in an increasingly complex environment will be challenged. This understanding can be achieved by engaging with the emerging science of Quality Improvement. In this paper we describe the medical profession's current approach to improving quality and assess where this approach has got us. We then compare current practice with an alternative approach which focuses not only on patients but also on the wider health system and we examine the opportunities and challenges that this presents to the medical profession.
Tendinopathy in volleyball elite players: prevalence of injuries, clinical and imaging evaluation
Authors: R Aido, M Massada, N Leitão, C Magalhães, J C Vasconcelos, J M Lourenço, N Puga
Journal: British Journal of Sports Medicine (2011)

Background High level volleyball players are at great risk of suffering rotator cuff and patellar tendinopathy. The symptoms are often serious resulting in long standing impairment of athletic performance. Objective The aim of this study was to estimate the prevalence of rotator cuff and patellar tendinopathy in volleyball elite players and correlate clinical examination with the changes observed with ultrasonography and power doppler (US+PD). Setting, participants and methods 20 Portuguese volleyball players from the senior national team, with mean age of 24.29 years and 11.14 years of average sports volleyball, were evaluated clinically and by US+PD. Results 80 evaluations were performed: 40 rotator cuff and 40 patellar tendons were assessed. Rotator cuff tendinopathy was diagnosed clinically in seven shoulders (17.50%), all in the dominant member. Eight rotator cuff tendons (20.00%) had structural changes and vascularity on US+PD. All the players with Jobe test painful had structural and vascularity changes on US+PD. Patellar tendinopathy was diagnosed clinically in 12 patellar tendons (30.00%), 6 on the dominant member. 20 tendons (50.00%) had structural changes and vascularity on US+PD. Only one player with patellar tendon palpation painful didn't have structural and vascularity changes on US+PD. According to the player position the opposites were the most affected players. Conclusions This research revealed that shoulder and knee are two frequent regions affected by overuses injuries in volleyball elite players. US+PD have good accuracy (with high sensibility) in confirming clinically diagnosed rotator cuff and patellar tendinopathy. The results reported in this study suggest that Jobe test and the palpation of patellar tendon are reliable tests in detecting rotator cuff and patellar tendinopathy.
Respiratory care units for non-invasive mechanical ventilation in motor neurone disease
Authors: E. SERVERA
Journal: Thorax (2000)

We read with interest the review by Polkey et al 1 pointing out the need to use all means possible to enable patients with motor neurone disease to achieve the best quality of life.

The authors state that, in order to maintain 24 hour ventilatory support, nasal ventilation must be complemented with alternative strategies during the day that are not suitable for widespread use in district general hospitals. We consider that it is possible to maintain 24 hour non-invasive ventilation in patients with …
Now let's have evidence based politics
Authors: T. Jackson
Journal: BMJ (2003)

Panorama: Fiddling the Figures BBC 1, 29 June at 10 15 pm http://news.bbc.co.uk/1/hi/programmes/panorama/3013062.stm Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> From education to health care, almost no area of the United Kingdom's public services seems spared New Labour's obsession with measuring achievement. If the consumer—be that patient, pupil, or commuter—is to get a better deal, then maybe some degree of target setting is a good thing. But in the NHS in particular, fears have been increasing that targets have been skewing priorities and encouraging short termism. Last month the Audit Commission claimed that hospitals had met government targets on waiting times and patient care through financial cunning, diverting money earmarked for services such as computers, medical equipment, and building maintenance ( BMJ 2003;326: 1229). Last Sunday's Panorama took up this theme and explored whether targets were harming the very people that they were meant to protect. The picture that emerged, through interviews with managers and clinicians in Oxford and London, was one of an NHS in which patients were being deceived. Hospitals … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Intestinal absorption in lysinuric protein intolerance: impaired for diamino acids, normal for citrulline.
Authors: J Rajantie, O Simell, J Perheentupa
Journal: Gut (1980)

Lysinuric protein intolerance (LPI) is an autosomal recessive defect of diamino acid transport characterised by massive diaminoaciduria, especially lysinuria, with hyperammonaemia after heavy nitrogen intake. The defect has previously been demonstrated in the kidney, and is probably present in the liver cells. To evaluate the effect of the LPI gene on the net intestinal absorption of the diamino acids and citrulline, separate oral loads of each were given to controls, and to subjects heterozygous and homozygous for LPI. In the affected subjects the plasma concentrations of the loaded diamino acids showed lower increments after the loads than in the controls, the difference being marked in the homozygotes and moderate in the heterozygotes. Urinary excretion failed to explain these differences. Thus, the diamino acid transport defect of LPI is also present in the intestine. After citrulline loads, in contrast, plasma citrulline levels rose similarly in controls and homozygotes. Thus, LPI is associated with intact citrulline absorption. The ornithinopenic hyperammonaemia of LPI is probably preventable by supplementing dietary protein with the ornithine precursor citrulline.
Antitumor Efficacy of a Combination of CMC-544 (Inotuzumab Ozogamicin), a CD22-Targeted Cytotoxic Immunoconjugate of Calicheamicin, and Rituximab against Non-Hodgkin's B-Cell Lymphoma
Authors: John F. DiJoseph, Maureen M. Dougher, Lyka B. Kalyandrug, Douglas C. Armellino, Erwin R. Boghaert, Philip R. Hamann, Justin K. Moran, Nitin K. Damle
Journal: Clinical Cancer Research (2006)

Abstract Purpose: CMC-544 is a CD22-targeted cytotoxic immunoconjugate, currently being evaluated in B-cell non-Hodgkin's lymphoma (B-NHL) patients. Rituximab is a CD20-targeted antibody commonly used in B-NHL therapy. Here, we describe antitumor efficacy of a combination of CMC-544 and rituximab against B-cell lymphoma (BCL) in preclinical models. Experimental Design: BCLs were cultured in vitro with CMC-544, rituximab, or their combination. BCLs were injected either s.c. or i.v. to establish localized s.c. BCL in nude mice or disseminated BCL in severe combined immunodeficient mice, respectively. I.p. treatment with CMC-544 or rituximab was initiated at various times either alone or in combination and its effect on s.c. BCL growth or survival of mice with disseminated BCL was monitored. Results: In vitro growth-inhibitory activity of CMC-544 combined with rituximab was additive. Rituximab but not CMC-544 exhibited effector functions, such as antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Rituximab was less effective in inhibiting growth of established BCL xenografts than developing xenografts. In contrast, CMC-544 was equally effective against both developing and established BCL xenografts. Although CMC-544 and rituximab individually caused partial inhibition of the growth of BCL xenografts at suboptimal doses examined, their combination suppressed xenograft growth by &amp;gt;90%. In a disseminated BCL model, 60% of CMC-544-treated mice and 20% of rituximab-treated mice survived for 125 days. In contrast, 90% of mice treated with the combination of CMC-544 and rituximab survived for longer than 125 days. Conclusion: The demonstration of superior antitumor activity of a combination of CMC-544 and rituximab described here provides the preclinical basis for its clinical evaluation as a treatment option for B-NHL.
Augmented Uptake of Neuraminidase-Treated Sheep Red Blood Cells: Participation of Opsonic Factors2
Authors: Jon R. Schmidtke, Richard L. Simmons
Journal: JNCI Journal of the National Cancer Institute (1975)

Neuraminidase from Vibrio cholerae (VCN) was used to treat sheep red blood cells (SRBC) which were then incubated in vitro with murine peritoneal macrophages. The uptake of VCN-treated SRBC by macrophages was greater than the uptake of SRBC not treated with VCN. SRBC opsonized with normal mouse serum (NMS) were taken up to a greater extent than untreated SRBC. SRBC treated with VCN and opsonized with NMS were phagocytosed to a greater extent than untreated SRBC, VCN-treated SRBC, or opsonized SRBC. Evidence demonstrated that factors in serum from normal C3H/HeJ mice augmented the uptake of VCN-treated SRBC in greater amounts than of normal SRBC. These findings were discussed in relation to the increased immunogenicity of neuraminidase-treated cells.
S95 Application of proteomics to explore the pathobiology of pulmonary arterial hypertension
Authors: V. B. Abdul-Salam, J. Wharton, M. R. Wilkins, R. J. Edwards
Journal: Thorax (2010)

<h3>Introduction and Objective</h3> Pulmonary arterial hypertension (PAH) is a poorly understood debilitating disorder which is characterised by increased resistance to the pulmonary blood flow caused by the remodelling of the pulmonary arteries. The objective of this study was to identify differentially expressed proteins in lungs of patients with PAH that may further help us understand the pathobiology of this disease. <h3>Methods</h3> Label-free liquid chromatography tandem mass spectrometry was used to generate protein expression profiles from the lung homogenates of 8 PAH patients and 8 Controls. Progenesis-MS software was then used to compare the relative levels of detected proteins. <h3>Results</h3> After application of stringent criteria to confirm proteins identities and to detect differences, 27 proteins were found to be differentially expressed from a total of 363 proteins. Proteins that had increased expression in PAH lungs were mainly involved in cell growth, proliferation and cell metabolism. Examples of affected proteins included chloride intracellular channel 4 (CLIC4) and periostin which were both up-regulated and these findings were confirmed by immunoblotting. CLIC4 is known to play a vital role in angiogenesis and has also been implicated in transforming growth factor-β, vascular endothelial growth factor and bone morphogenetic protein receptor two signalling pathways. Periostin is an extracellular matrix protein considered to be involved in vascular injury responses and regulation of smooth muscle cell proliferation. Immunohistochemistry studies showed predominant localisation of CLIC4 in the endothelium of remodelled pulmonary arteries and in plexiform lesions while periostin was prominent in the airways and in the neointimal layer of the remodelled pulmonary arteries. <h3>Conclusions</h3> Many proteins that may be involved in the pathogenesis of PAH have been discovered using label free proteomics. Examples include CLIC4 and periostin, which may be involved in the remodelling of vessels in PAH.
Alkhumra (Alkhurma) virus outbreak in Najran, Saudi Arabia: Epidemiological, clinical, and Laboratory characteristics
Authors: Tariq A. Madani, Esam I. Azhar, El-Tayeb M.E. Abuelzein, Mujahed Kao, Hussein M.S. Al-Bar, Huda Abu-Araki, Matthias Niedrig, Thomas G. Ksiazek
Journal: Journal of Infection (2010)
Hierarchies, similarity, and interactivity in object recognition: “Category-specific” neuropsychological deficits
Authors: Glyn W. Humphreys, Emer M. E. Forde
Journal: Behavioral and Brain Sciences (2001)

Category-specific impairments of object recognition and naming are among the most intriguing disorders in neuropsychology, affecting the retrieval of knowledge about either living or nonliving things. They can give us insight into the nature of our representations of objects: Have we evolved different neural systems for recognizing different categories of object? What kinds of knowledge are important for recognizing particular objects? How does visual similarity within a category influence object recognition and representation? What is the nature of our semantic knowledge about different objects? We review the evidence on category-specific impairments, arguing that deficits even for one class of object (e.g., living things) cannot be accounted for in terms of a single information processing disorder across all patients; problems arise at contrasting loci in different patients. The same apparent pattern of impairment can be produced by damage to different loci. According to a new processing framework for object recognition and naming, the hierarchical interactive theory (HIT), we have a hierarchy of highly interactive stored representations. HIT explains the variety of patients in terms of (1) lesions at different levels of processing and (2) different forms of stored knowledge used both for particular tasks and for particular categories of object.
Differential effects of renin-angiotensin system blockade on atherogenesis in cholesterol-fed rabbits.
Authors: J R Schuh, D J Blehm, G E Frierdich, E G McMahon, E H Blaine
Journal: Journal of Clinical Investigation (1993)

To investigate the mechanism by which angiotensin-converting enzyme (ACE) inhibition attenuates atherogenesis, we have studied the effects of a non-sulfhydryl ACE inhibitor, enalapril, and an angiotensin receptor antagonist, SC-51316, in cholesterol-fed rabbits. After 3 mo of enalapril treatment (10 mg/kg per d, p.o.) the percent plaque areas in the thoracic aortas of treated animals were significantly reduced (controls: 86.8 +/- 3.5%; treated: 31.1 +/- 8%, P < 0.001). Aortic cholesterol content was also reduced (controls: 31.4 +/- 3.2 mg/g tissue; treated: 7.4 +/- 1.8 mg/g, P < 0.001). Enalapril had no significant effect on plasma lipid levels or conscious blood pressure. In a second study, the angiotensin II receptor antagonist SC-51316 was administered at a dose equivalent to enalapril at blocking angiotensin pressor effects in vivo (30 mg/kg per d, p.o.). Evaluation after 3 mo indicated no significant attenuation of aortic atherosclerosis. These results demonstrate that: (a) enalapril attenuates atherogenesis without affecting either blood pressure or plasma lipid levels; (b) antioxidant activity, found with sulfhydryl-containing ACE inhibitors, is not necessary for reducing plaque formation; and (c) the attenuation of atherogenesis by ACE inhibition may not be due to blockade of the renin-angiotensin system. Alternatively, one must consider the multiple effects of ACE inhibition on other hormone systems, such as bradykinin, or the possibility that alternate angiotensin II receptors may be involved in atherosclerosis.
Impaired glucose tolerance and growth hormone in chronic liver disease.
Authors: W J Riley, V J McCann
Journal: Gut (1981)

Autoimmune Glomerulonephritis results in significant mortality and morbidity in numerous auto-inflammatory kidney diseases. The chronic inflammatory state is considered to be a driving force for AGN. In recent years the IL-23/Th17 axis appears to contribute to the pathogenesis of human and experimental AGN. However, the role of IL-17 receptor signaling in renal pathology associated with AGN is poorly defined. Here, using a murine model of accelerated experimental autoimmune glomerulonephritis, we showed that IL-17RA signaling is critical for the development of renal pathology and inflammatory changes in the kidney. Consequently, mice deficient in IL-17RA signaling exhibited diminished renal inflammation and infiltration of the innate effector cells in the kidney, correlating with the reduced expression of IL-17 responsive genes. IL-17 enhanced the production of proinflammatory cytokines and chemokines from tubular epithelial cells, which are implicated in the recruitment of innate effector cells in the kidney. Finally, neutralization of IL-17A ameliorated renal pathology in wild type mice following aEAGN induction. These results clearly demonstrated that IL-17RA signaling significantly contributes to renal tissue injury in AGN and suggest that blocking IL-17RA may be a promising therapeutic strategy for the treatment of proliferative and crescentic glomerulonephritis.
Sleep apnoea is associated with major cardiac events in peripheral arterial disease
Authors: Karri T. Utriainen, Juhani K. Airaksinen, Olli Polo, Ruut Laitio, Mikko J. Pietilä, Harry Scheinin, Tero Vahlberg, Kari A. Leino, Erkki S. Kentala, Jouko R. Jalonen, Harri Hakovirta, Riitta Parkkola, Sami Virtanen, Timo T. Laitio
Journal: European Respiratory Journal (2014)

Obstructive sleep apnoea (OSA) is associated with atherosclerosis and cardiovascular events. Peripheral arterial disease (PAD) represents severe atherosclerosis with a high mortality after vascular surgery. The role of OSA in the prognosis of these patients is not yet established. 84 patients (aged 67±9 years) scheduled for sub-inguinal surgical revascularisation were enrolled for preoperative polysomnography. The threshold for significant OSA was an apnoea/hypopnoea index ≥20 events·h −1 . Major adverse cardiovascular and cerebrovascular events (MACCE), including cardiac death, myocardial infarction, coronary revascularisation, angina pectoris requiring hospitalisation and stroke, were used as a combined end-point. During follow-up (median 52 months), 17 out of 39 patients with and six out of 45 patients without significant OSA suffered MACCE. In the multivariate Cox regression, the primary predictors of MACCE were significant OSA (hazard ratio (HR) 5.1 (95% CI 1.9–13.9); p=0.001) and pre-existing coronary artery disease (HR 4.4 (95% CI 1.8–10.6); p=0.001). Other significant predictors were a ≥4 year history of PAD (HR 3.8 (95% CI 1.3–11.5); p=0.02) and decreasing high-density lipoprotein/total cholesterol ratio (HR 0.95 per percentage (95% CI 0.90–1.00); p=0.048). OSA is associated with poor long-term outcome in patients with PAD following revascularisation. OSA might have an important role in the pathogenesis of cardiovascular morbidity and mortality in these patients.