tbuckley/cabot-search huggingface dataset:
The diagnostic value of scintigraphy in assessing sacroiliitis in ankylosing spondylitis: a systematic literature research
Authors: I H Song, J Carrasco-Fernandez, M Rudwaleit, J Sieper
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Background:</h3> The diagnostic value of scintigraphy in detecting sacroiliitis in patients with spondyloarthritis is not clear. <h3>Objective:</h3> To assess the diagnostic value of scintigraphy in detecting sacroiliitis in ankylosing spondylitis (AS) and in patients with clinically probable sacroiliitis without <i>x</i>-ray changes. <h3>Material and methods:</h3> A systematic literature research was performed in the Pubmed and Medline database up to August 2007. Articles in English and German on patients with established AS and clinically probable sacroiliitis without <i>x</i>-ray changes were selected. In addition, studies including patients with mechanical low back pain as a control group were searched. Pooled sensitivity, specificity and positive and negative likelihood ratios were calculated. <h3>Results:</h3> In total 99 articles about scintigraphy were found. 25 articles were included into the analysis. Overall sensitivity for scintigraphy to detect sacroiliitis was 51.8% for patients with established AS (n = 361) and 49.4% for patients with probable sacroiliitis (n = 255). Sensitivity of scintigraphy in patients with AS with inflammatory back pain (indicating ongoing inflammation) was 52.7% (n = 112) and in patients with AS and suspected sacroiliitis with magnetic resonance imaging showing acute sacroiliitis (as a gold standard) was 53.2% (n = 62). In controls with mechanical low back pain specificity was 78.3% (n = 60) resulting in likelihood ratios not higher than 2.5–3.0. <h3>Conclusion:</h3> These data as a result of a literature research suggest that scintigraphy of the sacroiliac joints is at most of limited diagnostic value for the diagnosis of established AS, including the early diagnosis of probable/suspected sacroiliitis.
Restoration and maintenance of glomerular filtration by mannitol during hypoperfusion of the kidney
Authors: C. Richard Morris, Edward A. Alexander, Frank J. Bruns, Norman G. Levinsky
Journal: Journal of Clinical Investigation (1972)

Glomerular filtration (GF) during progressive reduction of renal perfusion pressure by aortic clamping was studied in hydropenic rats and in rats infused with isotonic saline, hypertonic saline, or mannitol. As judged by visual observation of Lissamine green movements in superficial nephrons. GF was absent in hydropenic or saline-loaded rats at 40 mm Hg aortic pressure, but continued in some nephrons of all rats infused with mannitol and of some rats infused with hypertonic saline. Urine flow persisted only in rats infused with mannitol. By use of the qualitative Hanssen technique, it was found that all glomeruli in superficial and deep portions of the cortex were perfused at 40 mm Hg in all groups of rats. By the same method. GF continued in 1% of nephrons in hydropenic rats, 12% of nephrons in isotonic saline-loaded rats, and 78% of nephrons in rats infused with mannitol. By means of a quantitative Hanssen technique, GF was 5.8 nl/min per nephron in mannitol-infused rats and not measurable (< 0.5 nl) in hydropenic rats. Superficial and deep nephrons were similar in both qualitative and quantitative studies. Although urine flow did not persist in rats infused with hypertonic saline, GF was detected in four of seven studies by the Hanssen method (mean, 9.1 nl/min per nephron). In additional experiments, mannitol infused after perfusion pressure had already been lowered to 40 mm Hg in hydropenic rats reestablished urine flow and GF (mean, 9.8 nl/min). Furosemide, isotonic and hypertonic saline did not restart urine flow; however, GF (Lissamine green) was restarted by hypertonic saline. We conclude that mannitol can maintain or reestablish by an extratubular mechanism GF which otherwise would not occur during renal hypoperfusion. Hypertonic saline has a similar effect on GF in some cases, but urine flow is not maintained, implying complete reabsorption of filtrate.
Effect of Rapamycin on Mouse Chronic Lymphocytic Leukemia and the Development of Nonhematopoietic Malignancies in <i>Eμ-TCL1</i> Transgenic Mice
Authors: Nicola Zanesi, Rami Aqeilan, Alessandra Drusco, Mohamed Kaou, Cinzia Sevignani, Stefan Costinean, Laura Bortesi, Gaspare La Rocca, Pavel Koldovsky, Stefano Volinia, Rita Mancini, George Calin, Charles P. Scott, Yuri Pekarsky, Carlo M. Croce
Journal: Cancer Research (2006)

Abstract Chronic lymphocytic leukemia (CLL) is the most common leukemia in the world. The TCL1 gene, responsible for prolymphocytic T cell leukemia, is also overexpressed in human B cell malignancies and overexpression of the Tcl1 protein occurs frequently in CLL. Aging transgenic mice that overexpress TCL1 under control of the μ immunoglobulin gene enhancer, develop a CD5+ B cell lymphoproliferative disorder mimicking human CLL and implicating TCL1 in the pathogenesis of CLL. In the current study, we exploited this transgenic mouse to investigate two different CLL-related issues: potential treatment of CLL and characterization of neoplasms that accompany CLL. We successfully transplanted CLL cells into syngeneic mice that led to CLL development in the recipient mice. This approach allowed us to verify the involvement of the Tcl1/Akt/mTOR biochemical pathway in the disease by testing the ability of a specific pharmacologic agent, rapamycin, to slow CLL. We also showed that 36% of these transgenic mice were affected by solid malignancies, in which the expression of the Tcl1 protein was absent. These findings indicate that other oncogenic mechanism(s) may be involved in the development of solid tumors in Eμ-TCL1 transgenic mice. (Cancer Res 2006: 66(2): 915–20)
The Epithelial Cell Transforming Sequence 2, a Guanine Nucleotide Exchange Factor for Rho GTPases, Is Repressed by p53 via Protein Methyltransferases and Is Required for G1-S Transition
Authors: Ariane Scoumanne, Xinbin Chen
Journal: Cancer Research (2006)

Abstract The epithelial cell transforming sequence 2 (ECT2), a member of the Dbl family of guanine nucleotide exchange factor for Rho GTPases, is required for cytokinesis. The tumor suppressor p53 plays a crucial role in coordinating cellular processes, such as cell cycle arrest and apoptosis, in response to stress signals. Here, we showed that ECT2 is negatively regulated by wild-type p53 but not tumor-derived mutant p53 or other p53 family members. In addition, ECT2 is down-regulated in multiple cell lines by DNA damage agents and Nutlin-3, an MDM2 antagonist, in a p53-dependent manner. We also showed that the activity of the ECT2 promoter is repressed by wild-type p53, and to a lesser extent, by p21. In addition, the second activation domain in p53 is necessary for the efficient repression of ECT2. Importantly, we found that the ECT2 gene is bound by p53 in vivo in response to DNA damage and Nutlin-3 treatment. Furthermore, we provided evidence that inhibition of protein methyltransferases, especially arginine methyltransferases, relieve the repression of ECT2 induced by DNA damage or Nutlin-3 in a p53-dependent manner. Finally, we generated multiple cell lines in which ECT2 is inducibly knocked down and found that ECT2 knockdown triggers cell cycle arrest in G1. Taken together, we uncovered a novel function for ECT2 and provided a novel mechanism by which p53 represses gene expression via protein methyltransferases. (Cancer Res 2006; 66(12): 6271-9)
Survival Patterns in Patients With Hodgkin's Lymphoma With a Pre-Existing Hospital Discharge Diagnosis of Autoimmune Disease
Authors: Ola Landgren, Ruth M. Pfeiffer, Sigurdur Y. Kristinsson, Magnus Björkholm
Journal: Journal of Clinical Oncology (2010)

Purpose Autoimmune diseases (AIs) are associated with elevated risk for Hodgkin's lymphoma (HL); however, information on the interplay of AIs and HL on survival is sparse. Patients and Methods We evaluated survival patterns for 7,414 patients with HL in relation to a pre-existing hospital discharge diagnosis of an AI. We also assessed survival patterns in relation to a prior AI diagnosis among 29,240 population-based matched controls. Results Among female patients with HL with (v those without) a pre-existing AI, the 5-year and 10-year overall survival was 46.0% (63.3%) and 41.0% (51.9%); for males, the corresponding numbers were 48.5% (59.2%) and 43.6% (51.5%), respectively (P &lt; .001). Among female controls with (v those without) a pre-existing AI, the 5-year and 10-year overall survival was 79.1% (90.2%) and 67.2% (83.3%); for males, the corresponding numbers were 82.5% (90.3%) and 68.6% (81.6%), respectively (P &lt; .001). Female patients with HL with (v those without) a pre-existing AI had a 1.8-fold (range, 1.3- to 2.4-fold) increased relative risk of dying at 5 years of follow-up; for males, the corresponding excess relative risk of dying was 1.7-fold (range, 1.3- to 2.2-fold). Conclusion Patients with HL have an overall excellent outcome from treatment but also pose some of the most complex challenges of cancer survivorship due to many late effects (eg, second malignancies, thyroid disease, cardiovascular disease, and altered reproductive and sexual function). Our finding that patients with HL with a hospital discharge diagnosis of an AI have a substantially higher risk of dying, emphasizes that underlying chronic diseases, such as AIs, should be high of the list of survivorship concerns for clinicians that treat HL.
T4 Increased reticular basement membrane thickness but NOT airway smooth muscle in endobronchial biopsies of severe preschool wheezers
Authors: R. O'Reilly, T. Oates, J. Zhu, P. K. Jeffery, A. Bush, S. Saglani
Journal: Thorax (2010)

A 66-year-old man with a recent radiographic diagnosis of a parietal brain tumour presented with severe left thigh pain that prevented ambulation. On examination, his left anterior thigh was mildly swollen without erythema. Initial concern was for deep vein thrombosis in the setting of brain malignancy or necrotising soft tissue infection. Subsequent imaging and biopsies revealed methicillin sensitive <i>Staphylococcus aureus</i> (MSSA) pyomyositis of the left thigh and MSSA brain abscess.
SOX9 Is Expressed in Normal Prostate Basal Cells and Regulates Androgen Receptor Expression in Prostate Cancer Cells
Authors: Hongyun Wang, Nicole C. McKnight, Tao Zhang, Michael L. Lu, Steven P. Balk, Xin Yuan
Journal: Cancer Research (2007)

SOX9 is a member of the SOX [Sry-related high-mobility group (HMG) box] family of HMG DNA-binding domain transcription factors and is required for the development and differentiation of multiple cell lineages. This report shows that basal epithelial cells express SOX9 in normal prostate, with no detectable expression in luminal epithelial cells. In contrast, SOX9 is expressed in primary prostate cancers in vivo, at a higher frequency in recurrent prostate cancer and in prostate cancer cell lines (LNCaP, CWR22, PC3, and DU145). SOX9 message and protein levels in prostate cancer cells were increased by treatment with glycogen synthase kinase 3beta inhibitor (SB415286), and SOX9 was reduced when beta-catenin was down-regulated by small interfering RNA (siRNA), indicating that SOX9 expression in prostate cancer is regulated by Wnt/beta-catenin signaling. SOX9 bound specifically to androgen receptor (AR) DNA-binding domain glutathione S-transferase fusion proteins, and this interaction was dependent on a short peptide immediately COOH-terminal to the DNA-binding domain (the C-terminal extension), which is required for interactions between steroid hormone receptors and the architectural HMG proteins. Exogenous SOX9 expressed at high nonphysiologic levels decreased AR expression and activity; however, at lower levels, SOX9 increased AR protein expression. Significantly, down-regulation of SOX9 by siRNA in prostate cancer cells reduced endogenous AR protein levels, and cell growth indicating that SOX9 contributes to AR regulation and decreased cellular proliferation. These results indicate that SOX9 in prostate basal cells supports the development and maintenance of the luminal epithelium and that a subset of prostate cancer cells may escape basal cell requirements through SOX9 expression.
Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in <i>BRAF</i> <sup> <i>V600E</i> </sup> melanoma
Authors: Siwen Hu-Lieskovan, Stephen Mok, Blanca Homet Moreno, Jennifer Tsoi, Lidia Robert, Lucas Goedert, Elaine M. Pinheiro, Richard C. Koya, Thomas G. Graeber, Begoña Comin-Anduix, Antoni Ribas
Journal: Science Translational Medicine (2015)

MEK inhibition enhanced the antitumor activity of combined BRAF inhibition and immunotherapy.
The Harveian Lecture ON THE HEART BEFORE HARVEY: Delivered before the Harveian Society on March 20th, 1924
Authors: J. E. Frazer
Journal: BMJ (1924)

PARENTERAL AND ENTERAL INFECTIONS.In addition to the enteral causes of the niutritional disturbances of infancy there are parenteral ones, such as bronchitis, otitis mnedia, pyelitis, etc., in which the intes- tinal mucous membrane and the secretions are probably so affected that nutritional states develop.The treatment for parenteral affection consists, generally speaking, in treating the parenteral state, such as a catarrh of the lungs, after the disappearance of which the nutri- tional disturbance subsides.If in doubt as to whether the enteral nutritional state or the parenteral infection is the more important, it is essential to be guided chiefly by the weight cur've, and treat the case accordingly as already explained.Of enteral infectioxis which lhave to be dis- tinguished from the nutritional disturbances are typhoid fever, dysentery, etc.The infectious diarrhoeas will not react to food as do the nutritional disturbances. CONCLUSION.Reviewing the nutritional disturbances from the first conception of clinical entities to the present well defined states, we are impressed by the necessity for the closest possible observations of clinical facts, the dovetailing of which into their suitable pigeon-holes needs infinite care, patience, and accurate deduction.In the future as in the past much will be learned from scientific investigation as to the importance of metabolic processes with regard to a single substance (like urea) in one of the food states; but it would appear as if, generally speaking, more inductive information is likely to ensue from careful clinical and biochemical methods applied to all four states in the same investigation.This would make a valuable comparison between the four states themselves and normality.Slight or marked differences between these states are likely to suggest new lines of investigation on a broader scale, which may lead to a clearer conception of the processes involved than the one substance inivestigated.Ultimately we may find the necessity for increasing the number of states of nutritional disturbances.
Role of RyR2 Phosphorylation at S2814 During Heart Failure Progression
Authors: Jonathan L. Respress, Ralph J. van Oort, Na Li, Natale Rolim, Sayali S. Dixit, Angela deAlmeida, Niels Voigt, William S. Lawrence, Darlene G. Skapura, Kristine Skårdal, Ulrik Wisløff, Thomas Wieland, Xun Ai, Steven M. Pogwizd, Dobromir Dobrev, Xander H.T. Wehrens
Journal: Circulation Research (2012)

Increased activity of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is thought to promote heart failure (HF) progression. However, the importance of CaMKII phosphorylation of ryanodine receptors (RyR2) in HF development and associated diastolic sarcoplasmic reticulum Ca(2+) leak is unclear.Determine the role of CaMKII phosphorylation of RyR2 in patients and mice with nonischemic and ischemic forms of HF.Phosphorylation of the primary CaMKII site S2814 on RyR2 was increased in patients with nonischemic, but not with ischemic, HF. Knock-in mice with an inactivated S2814 phosphorylation site were relatively protected from HF development after transverse aortic constriction compared with wild-type littermates. After transverse aortic constriction, S2814A mice did not exhibit pulmonary congestion and had reduced levels of atrial natriuretic factor. Cardiomyocytes from S2814A mice exhibited significantly lower sarcoplasmic reticulum Ca(2+) leak and improved sarcoplasmic reticulum Ca(2+) loading compared with wild-type mice after transverse aortic constriction. Interestingly, these protective effects on cardiac contractility were not observed in S2814A mice after experimental myocardial infarction.Our results suggest that increased CaMKII phosphorylation of RyR2 plays a role in the development of pathological sarcoplasmic reticulum Ca(2+) leak and HF development in nonischemic forms of HF such as transverse aortic constriction in mice.
Binding Characteristics of Myosin and F-Actin from Dog Hearts
Authors: GENE CONWOY, ROBERT HEAZLITT, JOE L. ROBERTS, LEROY STEWART
Journal: Circulation Research (1969)

We used light scattering and ultracentrifugation to study the binding ratio of myosin and actin from normal and failing dog hearts and to determine the effect of temperature and adenosine triphosphate (ATP) on the binding. For comparison, similar studies were done on myosin and actin from rabbit skeletal muscle. We found a higher combining ratio, by weight, for cardiac myosin and actin (4.8 : 1) than for skeletal myosin and actin (4.4 : 1). The dissociation constants were similar at 24°C for cardiac and skeletal proteins. But at 10°C, the dissociation constant was greater for cardiac proteins, and the difference appeared more pronounced when phosphate was used to buffer the solutions. The dissociation constant at 10°C was greater for myosin and actin from failing dog hearts. ATP caused dissociation of cardiac and skeletal F-acto-heavy meromyosin and F-actomyosin. There was evidence that the binding of cardiac proteins may not be as tight as that of skeletal muscle proteins.
Tools evolve: The artificial selection and evolution of Paleolithic stone tools
Authors: Jorge Simão
Journal: Behavioral and Brain Sciences (2002)

I claim that the increase in complexity in the (known) trace of Paleolithic stone tools can be parsimoniously explained by postulating the emergence of effective mechanisms for the social transmission of representations. I propose that Paleolithic tools, similar to more contemporary tools, were subject to a process of evolution by artificial selection based on functionality.
Whole-genome sequence of a flatfish provides insights into ZW sex chromosome evolution and adaptation to a benthic lifestyle
Authors: Songlin Chen, Guojie Zhang, Changwei Shao, Quanfei Huang, Geng Liu, Pei Zhang, Wentao Song, Na An, Domitille Chalopin, Jean-Nicolas Volff, Yunhan Hong, Qiye Li, Zhenxia Sha, Heling Zhou, Mingshu Xie, Qiulin Yu, Yang Liu, Hui Xiang, Na Wang, Kui Wu, Changgeng Yang, Qian Zhou, Xiaolin Liao, Linfeng Yang, Qiaomu Hu, Jilin Zhang, Liang Meng, Lijun Jin, Yongsheng Tian, Jinmin Lian, Jingfeng Yang, Guidong Miao, Shanshan Liu, Zhuo Liang, Fang Yan, Yangzhen Li, Bin Sun, Hong Zhang, Jing Zhang, Ying Zhu, Min Du, Yongwei Zhao, Manfred Schartl, Qisheng Tang, Jun Wang
Journal: Nature Genetics (2014)

Songlin Chen and colleagues sequenced the whole genomes of a male (ZZ) and a female (ZW) Chinese half-smooth tongue sole, Cynoglossus semilaevis. Their analysis provides insights into the structure and evolution of the sex chromosomes and adaptation to the benthic lifestyle of this flatfish. Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.
Patent Foramen Ovale Closure — Closing the Door Except for Trials
Authors: S. Claiborne Johnston
Journal: New England Journal of Medicine (2012)

Patent foramen ovale is a well established cause of stroke. A thrombus from venous structures can embolize through a patent foramen ovale1 and ultimately reach the brain.2 However, a patent foramen ovale can also be present in 25% of healthy people. Although detected in nearly twice as many patients with stroke of no other identifiable cause,3 a patent foramen ovale will be an incidental finding in many patients who present with stroke, given the frequency of this defect in the background population.Several devices designed to occlude a patent foramen ovale and atrial septal defects are currently on the market. . . .
Indoor air pollution and childhood asthma: effective environmental interventions.
Authors: R A Etzel
Journal: Environmental Health Perspectives (1995)

Exposure to indoor air pollutants such as tobacco smoke and dust mites may exacerbate childhood asthma. Environmental interventions to reduce exposures to these pollutants can help prevent exacerbations of the disease. Among the most important interventions is the elimination of environmental tobacco smoke from the environments of children with asthma. However, the effectiveness of reducing asthmatic children's exposure to environmental tobacco smoke on the severity of their symptoms has not yet been systematically evaluated. Dust mite reduction is another helpful environmental intervention. This can be achieved by enclosing the child's mattresses, blankets, and pillows in zippered polyurethane-coated casings. Primary prevention of asthma is not as well understood. It is anticipated that efforts to reduce smoking during pregnancy could reduce the incidence of asthma in children. European studies have suggested that reducing exposure to food and house dust mite antigens during lactation and for the first 12 months of life diminishes the development of allergic disorders in infants with high total IgE in the cord blood and a family history of atopy. Many children with asthma and their families are not receiving adequate counseling about environmental interventions from health care providers or other sources.
Epidermal Innervation in Type 1 Diabetic Patients
Authors: Petr Boucek, Terezia Havrdova, Ludek Voska, Alena Lodererova, Lan He, Frantisek Saudek, Kvetoslav Lipar, Milos Adamec, Claudia Sommer
Journal: Diabetes Care (2008)

OBJECTIVE—To assess the effect of normoglycemia following simultaneous pancreas/kidney transplantation (SPK) on neurological function and intraepidermal nerve fiber density (IENFD) in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—We performed vibration perception threshold (VPT) testing and autonomic function testing (AFT) and assessed IENFD in skin biopsies from the lower thigh and upper calf in 14 healthy control subjects and 18 patients with type 1 diabetes at the time of and at 21–40 (median 29) months post SPK. RESULTS—At baseline, significantly increased VPTs, pathological AFT results, and severe reduction in IENFD were present in SPK recipients. After SPK, an increase of IENFD in the thigh of more than one epidermal nerve fiber per millimeter was noted in three patients (median 4.1, range 1.9–10.2), but changes were not significant for the group as a whole. CONCLUSIONS—We conclude that either irreversible nerve damage might be present in some SPK recipients or that longer periods of normoglycemia might be needed to allow nerve regeneration.