tbuckley/cabot-search huggingface dataset:
Identification of a gC1q-binding protein (gC1q-R) on the surface of human neutrophils. Subcellular localization and binding properties in comparison with the cC1q-R.
Authors: P Eggleton, B Ghebrehiwet, K N Sastry, J P Coburn, K S Zaner, K B Reid, A I Tauber
Journal: Journal of Clinical Investigation (1995)

Human neutrophils have multiple C1q-binding proteins. Direct ligand-binding studies with the globular domain of C1q and two-dimensional Western blot analysis revealed two gC1q-binding proteins (gC1q-R): a 33,000 M(r) protein (pI 4.5) mainly in the neutrophil plasma membrane and an 80,000-90,000 M(r) protein (pI 4.1-4.2) located mainly in the granules. Direct binding studies showed that C1q bound to this higher molecular weight protein under physiological conditions. In contrast, anti-cC1q-R antibody, which recognizes a protein binding to collagenous tails of C1q, detected only a 68,000 M(r) protein in the plasma membrane. Both the 33,000 and 68,000 M(r) receptors appear early on the surface of differentiating HL-60 cells. On mature neutrophils, surface expression of both C1q receptors was evident, but no upregulation was observed upon stimulation. Phorbol myristate acetate treatment of neutrophils downregulated both the receptors from cell surface, and significant amounts of soluble gC1q-R were in cell media supernatants, suggesting receptor shedding or secretion. gC1q-R, unlike cC1q-R, did not bind to other C1q-like ligands, namely mannose binding protein, surfactant protein-A, surfactant protein-D, or conglutinin under normal ionic conditions, suggesting a greater specificity for C1q than the "collectin" type receptor (cC1q-R). Rather, gC1q-R only bound purified C1q, and the binding was enhanced under low ionic conditions and in the absence of calcium. The role of C1q receptor shedding and its biologic consequence remain to be defined, but may contribute to the diversity of C1q-mediated responses observed in many cell types.
EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: Prevalence of inflammation in osteoarthritis
Authors: M A D'Agostino
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To assess the prevalence of inflammation in subjects with chronic painful knee osteoarthritis (OA), as determined by the presence of synovitis or joint effusion at ultrasonography (US); and to evaluate the correlation between synovitis, effusion, and clinical parameters. <b>Methods:</b> A cross sectional, multicentre, European study was conducted under the umbrella of EULAR-ESCISIT. Subjects had primary chronic knee OA (ACR criteria) with pain during physical activity ⩾30 mm for at least 48 hours. Clinical parameters were collected by a rheumatologist and an US examination of the painful knee was performed by a radiologist or rheumatologist within 72 hours of the clinical examination. Ultrasonographic synovitis was defined as synovial thickness ⩾4 mm and diffuse or nodular appearance, and a joint effusion was defined as effusion depth ⩾4 mm. <b>Results:</b> 600 patients with painful knee OA were analysed. At US 16 (2.7%) had synovitis alone, 85 (14.2%) had both synovitis and effusion, 177 (29.5%) had joint effusion alone, and 322 (53.7%) had no inflammation according to the definitions employed. Multivariate analysis showed that inflammation seen by US correlated statistically with advanced radiographic disease (Kellgren-Lawrence grade ⩾3; odds ratio (OR) = 2.20 and 1.91 for synovitis and joint effusion, respectively), and with clinical signs and symptoms suggestive of an inflammatory "flare", such as joint effusion on clinical examination (OR = 1.97 and 2.70 for synovitis and joint effusion, respectively) or sudden aggravation of knee pain (OR = 1.77 for joint effusion). <b>Conclusion:</b> US can detect synovial inflammation and effusion in painful knee OA, which correlate significantly with knee synovitis, effusion, and clinical parameters suggestive of an inflammatory "flare".
Effects of exercise on the autonomic control of the heart: training or overtraining?
Authors: M. Piepoli, A. J S Coats
Journal: Cardiovascular Research (1994)

Journal Article Effects of exercise on the autonomic control of the heart: training or overtraining? Get access Massimo Piepoli, Massimo Piepoli Search for other works by this author on: Oxford Academic PubMed Google Scholar Andrew J S Coats Andrew J S Coats Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 1, January 1994, Pages 141–142, https://doi.org/10.1093/cvr/28.1.141 Published: 01 January 1994
Androgen-Induced <i>TMPRSS2:ERG</i> Fusion in Nonmalignant Prostate Epithelial Cells
Authors: Nuria Coll Bastus, Lara K. Boyd, Xueying Mao, Elzbieta Stankiewicz, Sakunthala C. Kudahetti, R. Tim D. Oliver, Daniel M. Berney, Yong-Jie Lu
Journal: Cancer Research (2010)

Abstract Fusion genes play important roles in tumorigenesis. The identification of the high-frequency TMPRSS2 fusion with ERG and other ETS family genes in prostate cancer highlights the importance of fusion genes in solid tumor development and progression. However, the mechanisms leading to these fusions are unclear. We investigated whether androgen, through stimulating its receptor, could promote spatial genome reorganization and contribute to the generation of the TMPRSS2:ERG fusion. We show that treatment with androgen can induce the TMPRSS2:ERG fusion in both malignant and nonmalignant prostate epithelial cells. Although the fusion could be detected in malignant cells following 24-hour treatment, prolonged exposure to androgen was required to detect the fusion transcript in nonmalignant cells. We associated the fusion incidence with genetic factors, including androgen-induced gene proximity, androgen receptor exon1 CAG repeat length and expression of the PIWIL1 gene. This study demonstrates that fusions can be induced prior to malignant transformation and generation of the fusion is associated with both gene proximity and loss of the ability to prevent double-strand breaks. Cancer Res; 70(23); 9544–8. ©2010 AACR.
G6PD Deficiency Prevalence and Estimates of Affected Populations in Malaria Endemic Countries: A Geostatistical Model-Based Map
Authors: Rosalind E. Howes, Frédéric B. Piel, Anand P. Patil, Oscar A. Nyangiri, Peter W. Gething, Mewahyu Dewi, Mariana M. Hogg, Katherine E. Battle, Carmencita D. Padilla, J. Kevin Baird, Simon I. Hay
Journal: PLoS Medicine (2012)

Primaquine is a key drug for malaria elimination. In addition to being the only drug active against the dormant relapsing forms of Plasmodium vivax, primaquine is the sole effective treatment of infectious P. falciparum gametocytes, and may interrupt transmission and help contain the spread of artemisinin resistance. However, primaquine can trigger haemolysis in patients with a deficiency in glucose-6-phosphate dehydrogenase (G6PDd). Poor information is available about the distribution of individuals at risk of primaquine-induced haemolysis. We present a continuous evidence-based prevalence map of G6PDd and estimates of affected populations, together with a national index of relative haemolytic risk.Representative community surveys of phenotypic G6PDd prevalence were identified for 1,734 spatially unique sites. These surveys formed the evidence-base for a Bayesian geostatistical model adapted to the gene's X-linked inheritance, which predicted a G6PDd allele frequency map across malaria endemic countries (MECs) and generated population-weighted estimates of affected populations. Highest median prevalence (peaking at 32.5%) was predicted across sub-Saharan Africa and the Arabian Peninsula. Although G6PDd prevalence was generally lower across central and southeast Asia, rarely exceeding 20%, the majority of G6PDd individuals (67.5% median estimate) were from Asian countries. We estimated a G6PDd allele frequency of 8.0% (interquartile range: 7.4-8.8) across MECs, and 5.3% (4.4-6.7) within malaria-eliminating countries. The reliability of the map is contingent on the underlying data informing the model; population heterogeneity can only be represented by the available surveys, and important weaknesses exist in the map across data-sparse regions. Uncertainty metrics are used to quantify some aspects of these limitations in the map. Finally, we assembled a database of G6PDd variant occurrences to inform a national-level index of relative G6PDd haemolytic risk. Asian countries, where variants were most severe, had the highest relative risks from G6PDd.G6PDd is widespread and spatially heterogeneous across most MECs where primaquine would be valuable for malaria control and elimination. The maps and population estimates presented here reflect potential risk of primaquine-associated harm. In the absence of non-toxic alternatives to primaquine, these results represent additional evidence to help inform safe use of this valuable, yet dangerous, component of the malaria-elimination toolkit. Please see later in the article for the Editors' Summary.
Ursodeoxycholic acid improves muscle contractility and inflammation in symptomatic gallbladders with cholesterol gallstones
Authors: M. P. L. Guarino, P. Cong, M. Cicala, R. Alloni, S. Carotti, J. Behar
Journal: Gut (2006)

To examine the mechanisms of action of ursodeoxycholic acid (UDCA) on gallbladder (GB) muscle cells in patients with symptomatic cholesterol gallstones (GSs) as it reduces the incidence of acute cholecystitis.
The relevance of circulating epithelial tumor cells (CETC) for therapy monitoring during neoadjuvant (primary systemic) chemotherapy in breast cancer
Authors: O. Camara, M. Rengsberger, A. Egbe, A. Koch, M. Gajda, U. Hammer, C. Jörke, C. Rabenstein, M. Untch, K. Pachmann
Journal: Annals of Oncology (2007)
Stimulation of thermogenesis by carbohydrate overfeeding. Evidence against sympathetic nervous system mediation.
Authors: S Welle, R G Campbell
Journal: Journal of Clinical Investigation (1983)

Daily carbohydrate intake of seven men with normal weight was limited to 220-265 g/d for 6 d and then increased to 620-770 g/d for 20 d, while intake of protein, fat, and sodium remained constant. Carbohydrate overfeeding increased body weight by 4.8%, basal oxygen consumption (VO2) by 7.4%, BMR by 11.5%, and serum triiodothyronine levels by 32%. Overfeeding did not affect the thermic effect of a standard meal. Intravenous propranolol reduced the thermic effect of a meal by 22% during the base-line feeding period, and by 13% during carbohydrate overfeeding, but did not affect preprandial VO2. Overfeeding attenuated the rise in plasma glucose and FFA levels induced by infusion of norepinephrine, but had no effect on the increase in VO2 induced by norepinephrine. Overfeeding did not alter 24-h urinary excretion of vanillylmandelic acid, supine plasma catecholamine levels (pre- and postprandial), blood pressure, or plasma renin activity, but increased peak standing plasma norepinephrine levels by 45% and resting pulse rate by 9%. Even though short-term carbohydrate overfeeding may produce modest stimulation of sympathetic nervous system activity in man, the increase in thermogenesis induced by such overfeeding is neither suppressed by beta adrenergic blockade nor accompanied by an increased sensitivity to the thermogenic effects of norepinephrine. These data do not support an important role for the sympathetic nervous system in mediating the thermogenic response to carbohydrate overfeeding.
Role of Kupffer cells and the spleen in modulation of endotoxin-induced liver injury after partial hepatectomy
Authors: S Suzuki
Journal: Hepatology (1996)

The hypothesis that both activated Kupffer cells and the spleen may be responsible for endotoxin-induced liver injury following partial hepatectomy was investigated. Male rats were divided into a sham group receiving laparotomy alone and three groups receiving a two-thirds hepatectomy; one group was given normal saline (NS) solution as a vehicle control, one group received intravenous gadolinium chloride (GC group) (7 mg/kg body weight) for 2 days before intravenous injection of endotoxin to inhibit Kupffer cell phagocytosis, and the third group simultaneously underwent splenectomy and partial hepatectomy (SH group). As endotoxin, lipopolysaccharide (LPS) (1 mg/kg body weight) was administered intravenously 2 days after surgery. In the GC and SH groups, phagocytic activity was reduced to approximately 40% of that in the sham group. The highest plasma tumor necrosis factor alpha (TNF-alpha) level (8,544 ± 1,223 pg/mL) was observed in the NS group at 1 hour after LPS administration, and the level was significantly reduced by GdCl3 or splenectomy (P < 0.05). Inhibition of Kupffer cell function and splenectomy attenuated functional and structural liver damage associated with the decreased hepatic infiltration of polymorphonuclear leukocytes (PMNs) and reduced priming of circulating PMNs in the early stage of endotoxemia following partial hepatectomy. Consequently, the 24-hour survival rate of the SH and GC groups was significantly improved to 50% and 80%, respectively (P < .05), while that of the NS group was 12.5%. These findings indicate that the modification of inflammatory mediator generation by splenectomy or inhibition of Kupffer cell function may be beneficial for the prevention of endotoxin-induced liver injury after partial hepatectomy.
Interferon-β Treatment Eliminates Cardiotropic Viruses and Improves Left Ventricular Function in Patients With Myocardial Persistence of Viral Genomes and Left Ventricular Dysfunction
Authors: Uwe Kühl, Matthias Pauschinger, Peter Lothar Schwimmbeck, Bettina Seeberg, Conny Lober, Michel Noutsias, Wolfgang Poller, Heinz-Peter Schultheiss
Journal: Circulation (2003)

Background— Viral infections are important causes of myocarditis and may induce cardiac dysfunction and finally lead to dilated cardiomyopathy. We investigated whether interferon (IFN)-β therapy is safe and may achieve virus clearance and prevent deterioration of left ventricular (LV) function in patients with myocardial virus persistence. Methods and Results— In this phase II study, 22 consecutive patients with persistence of LV dysfunction (history of symptoms, 44±27 months) and polymerase chain reaction–proven enteroviral or adenoviral genomes were treated with 18×10 6 IU/week IFN-β (Beneferon) subcutaneously for 24 weeks. Histological and immunohistological analysis of endomyocardial biopsies was used to characterize myocardial inflammation. LV diameters and ejection fraction were assessed by echocardiography and angiography, respectively. During the treatment period, IFN-β was well tolerated by all patients. No patient deteriorated. Clearance of viral genomes was observed in 22 of 22 of patients after antiviral therapy. Virus clearance was paralleled by a significant decrease of LV end diastolic and end systolic diameters, decreasing from 59.7±11.1 to 56.5±10.0 mm ( P &lt;0.001) and 43.2±13.6 to 39.4±12.1 mm ( P &lt;0.001), respectively. LV ejection fraction increased from 44.6±15.5% to 53.1±16.8% ( P &lt;0.001). Conclusions— A 6 months, IFN-β treatment was safe in patients with myocardial enteroviral or adenoviral persistence and LV dysfunction and resulted in elimination of viral genomes (22 of 22 patients) and improved LV function (15 of 22 patients).
The Effectiveness of Off-Protocol Adjuvant Chemotherapy for Patients with Urothelial Carcinoma of the Urinary Bladder
Authors: Robert S. Svatek, Shahrokh F. Shariat, Robert E. Lasky, Eila C. Skinner, Giacomo Novara, Seth P. Lerner, Yves Fradet, Patrick J. Bastian, Wassim Kassouf, Pierre I. Karakiewicz, Hans-Martin Fritsche, Stefan C. Müller, Jonathan I. Izawa, Vincenzo Ficarra, Arthur I. Sagalowsky, Mark P. Schoenberg, Arlene O. Siefker-Radtke, Randall E. Millikan, Colin P.N. Dinney
Journal: Clinical Cancer Research (2010)

The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing radical cystectomy for UCB in an off-protocol routine clinical setting.We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy. Patients were grouped into quintiles based on their risk of disease progression using estimates from a fitted multivariable Cox proportional hazards model. The association of adjuvant chemotherapy with survival was explored across separate quintiles.The cohort consisted of 3,947 patients, 932 (23.6%) of whom received adjuvant chemotherapy. Adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.83; 95% confidence interval, 0.72-0.97%, P = 0.017). However, the effect of adjuvant chemotherapy was significantly modified by the individual's risk of disease progression such that an increasing benefit from adjuvant chemotherapy was seen across higher-risk subgroups (P < 0.001). There was a significant improvement in survival between the treated and nontreated patients in the highest-risk quintile (hazard ratio, 0.75; 95% confidence interval, 0.62-0.90; P = 0.002). This group was characterized by an estimated 32.8% 5-year probability of cancer-specific survival, with 86.6% of patients having both advanced pathologic stage (> or =T(3)) and nodal involvement.Adjuvant chemotherapy is associated with a significant improvement in survival for patients treated in an off-protocol clinical setting. Selective administration in patients at the highest risk for disease progression, such as those with advanced pathologic stage and nodal involvement, may optimize the therapeutic benefit of adjuvant chemotherapy.
Relative Contribution of Residual Renal Function and Different Measures of Adequacy to Survival in Hemodialysis Patients
Authors: Fabian Termorshuizen, Friedo W. Dekker, Jeannette G. van Manen, Johanna C. Korevaar, Elisabeth W. Boeschoten, Raymond T. Krediet
Journal: Journal of the American Society of Nephrology (2004)

A high delivered Kt/V(urea) (dKt/V(urea)) is advocated in the U.S. National Kidney Foundation Dialysis Outcomes Quality Initiative guidelines on hemodialysis (HD) adequacy, irrespective of the presence of residual renal function. The contribution of treatment adequacy and residual renal function to patient survival was investigated. The Netherlands Cooperative Study on the Adequacy of Dialysis is a prospective multicenter study that includes incident ESRD patients older than 18 yr. The longitudinal data on residual renal function and dialysis adequacy of patients who were treated with HD 3 mo after the initiation of dialysis (n = 740) were analyzed. The mean renal Kt/V(urea) (rKt/V(urea)) at 3 mo was 0.7/wk (SD 0.6) and the dKt/V(urea) at 3 mo was 2.7/wk (SD 0.8). Both components of urea clearance were associated with a better survival (for each increase of 1/wk in rKt/V(urea), relative risk of death = 0.44 [P < 0.0001]; dKt/V(urea), relative risk of death = 0.76 [P < 0.01]). However, the effect of dKt/V(urea) on mortality was strongly dependent on the presence of rKt/V(urea), low values for dKt/V(urea) of <2.9/wk being associated with a significantly higher mortality in anuric patients only. Furthermore, an excess of ultrafiltration in relation to interdialytic weight gain was associated with an increase in mortality independent of dKt/V(urea). In conclusion, residual renal clearance seems to be an important predictor of survival in HD patients, and the dKt/V(urea) should be tuned appropriately to the presence of renal function. Further studies are required to substantiate the important role of fluid balance in HD adequacy.
Zinc Protoporphyrin and Iron Deficiency Screening
Authors: Hema Magge, Philippa Sprinz, William G. Adams, Mari-Lynn Drainoni, Alan Meyers
Journal: JAMA Pediatrics (2013)

Iron deficiency is the most common micronutrient deficiency among children worldwide, with iron-deficiency anemia associated with long-term adverse neurodevelopmental effects.To understand the role of zinc protoporphyrin (ZPP) in iron deficiency screening in a low-income pediatric population, as well as to describe the prevalence and trends of abnormal ZPP and the response to iron therapy.Retrospective longitudinal study of data from electronic medical records collected from January 1, 2002, through December 31, 2010.Boston Medical Center primary care center.A total of 2612 children with baseline routine screening results for complete blood cell count, lead, and ZPP drawn between ages 8 and 18 months and at follow-up were included. Children with sickle cell disease or lead toxicity were excluded.Documented iron prescription.Reduction of baseline abnormal ZPP at follow-up.Of 2612 children, 48% had an abnormal ZPP level at baseline. Among those with abnormal ZPP (n = 1254), 18% were prescribed iron. Iron prescription was significantly associated with ZPP reduction (odds ratio, 1.5; 95% CI, 1.1 to 2.0) and greater mean change in ZPP (mean difference, -4.4; 95% CI, -7.2 to -1.5). In multivariate analysis, the effect of iron prescription on the reduction of abnormal ZPP was modified by hemoglobin level. Iron prescription was significantly associated with ZPP reduction among those with anemia (odds ratio, 2.4; 95% CI, 1.1 to 5.0). Iron was rarely prescribed in children without anemia; a substantial, but not statistically significant, trend to improvement in those prescribed iron with low-normal hemoglobin was found.Abnormal ZPP was common in this low-income population. Iron prescription was significantly associated with a larger reduction of ZPP. Our data suggest that ZPP may be appropriate for iron deficiency screening; further investigation is warranted to explore the role of ZPP among nonanemic children.
Performance enhanced headgear: a scientific approach to the development of protective headgear
Authors: A McIntosh, P McCrory, C F Finch
Journal: British Journal of Sports Medicine (2004)

Background: There is a continuing debate about the performance of protective headgear in rugby union, rugby league, and Australian rules football. Objectives: To examine the impact energy attenuation performance of foam that could be incorporated into headgear and examine the performance of prototypes of modified headgear. Methods: Impact tests were conducted on polyethylene foams and protective headgear. Free fall drop tests with a rigid headform on to a flat rigid anvil were conducted. Resultant headform acceleration was measured. Means of the headform acceleration maxima for repeat tests were calculated. Results: Tests on polyethylene foam indicated that an increase in thickness from 10 mm to 16 mm would improve headgear performance. These modifications were incorporated in part into two headgear models: the Albion Headpro and the Canterbury brand Body Armour honeycomb headgear. The headgear tests show that significant reductions in headform acceleration were achieved by increasing the foam density and thickness. Mean headform acceleration maxima for the 16 mm thick modified rugby headgear was about 25% of that of standard headgear for lateral impact 0.3 and 0.4 m drop heights and 27% for the centre front 0.3 m drop tests. At these impacts, the headform acceleration for the modified rugby headgear was below 200 g . Conclusions: Significant improvements in impact energy attenuation performance are possible with small design changes. Whether these are sufficient to reduce the rate or severity of concussion in rugby and Australian rules football can only be shown by formal prospective studies on the field.