tbuckley/cabot-search huggingface dataset:
Short-Term Medical Benefits and Adverse Effects of Weight Loss
Authors: F. Xavier Pi-Sunyer
Journal: Annals of Internal Medicine (1993)

Weight loss reduces many of the health hazards associated with obesity including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, sleep apnea, hypoxemia and hypercarbia, and osteoarthritis. Potential adverse effects of weight loss include a greater risk for gallstone formation and cholecystitis, excessive loss of lean body mass, water and electrolyte problems, mild liver dysfunction, and elevated uric acid levels. Less consequential problems such as diarrhea, constipation, hair loss, and cold intolerance may also occur. The short-term adverse effects are not severe enough to contraindicate weight loss, nor do they outweigh its short-term benefits.
Rac Activation Is Associated with Hepatocellular Carcinoma Metastasis by Up-regulation of Vascular Endothelial Growth Factor Expression
Authors: Terence K. Lee, Ronnie T.P. Poon, Anthony P. Yuen, Kwan Man, Zhen Fan Yang, Xin Yuan Guan, Sheung Tat Fan
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Hepatocellular carcinoma (HCC) is associated with a propensity for vascular invasion and metastasis, which contribute to poor prognosis. Angiogenesis is a crucial process contributing to tumor growth and metastasis. Recently, Rac has been suggested to play a role in angiogenesis. However, the actual role of Rac in HCC angiogenesis remains unclear. Given that vascular endothelial growth factor (VEGF) is an important angiogenic factor in HCC, the purpose of this study was to evaluate the possible correlation between Rac activation and VEGF expression in HCC tumor samples, as well as the mechanism involved in Rac-induced HCC angiogenesis. Experimental Design: We evaluated Rac and VEGF expression in the HCC tissue microarray of paired primary and metastatic HCC samples using immunohistochemical staining. The role of Rac-induced HCC angiogenesis was also evaluated in vitro in HCC cell lines. Results: We first showed that activation of Rac was correlated with HCC metastasis (P &amp;lt; 0.001), and its expression was significantly correlated with VEGF expression by tissue microarray. Ectopic Rac-dominant active transfection in Hep3B cells increased VEGF secretion, which induced the morphologic change and proliferation of human umbilical vein endothelial cells, resulting in the promotion of angiogenesis. Rac induced the transcriptional activation of VEGF by direct interaction with hypoxia-inducible factor-1α (HIF-1α) expression. In hypoxic conditions, Rac promoted angiogenesis through an increase in HIF-1α stabilization. Conclusion: This study shows that Rac is a novel angiogenic factor for HCC through the enhancement of HIF-1α protein stability, which provides a possible therapeutic target in the development of inhibitors of angiogenesis.
A new variable stiffness colonoscope makes colonoscopy easier: a randomised controlled trial
Authors: J C Brooker
Journal: Gut (2000)

<h3>BACKGROUND</h3> Colonoscopy remains technically difficult in 10–20% of procedures due to variable colonic anatomy and fixation. The ability to vary endoscope shaft flexibility may help insertion to the caecum. <h3>METHODS</h3> Consecutive patients attending for day case colonoscopy were randomised to examination with either the conventional Olympus CF200HL (200HL) or a new variable stiffness (VS) colonoscope. Intubation time, use of stiffening function, and patient pain scores were compared. <h3>RESULTS</h3> Of 100 cases, 43 were performed with the 200HL and 57 with the VS. Four incomplete examinations occurred with the 200HL (two sigmoid fixations, two benign strictures) and two with the VS (one obstructing cancer, one fixed sigmoid). Changing to the paediatric scope was successful in all but one patient from each group (obstructive lesions). Stiff mode was applied 23 times in 18 patients and was effective in 15 of these. Intubation time was quicker with the VS (median 6 minutes 32 seconds) than with the 200HL (median 10 minutes 35 seconds) (p=0.0005). Pain scores were less with the VS (median 7) than with the 200HL (median 24) (p=0.0081). <h3>CONCLUSIONS</h3> The variable stiffness colonoscope combines paediatric shaft characteristics with the ability to stiffen when needed. This instrument significantly reduces intubation time and patient discomfort. Further comparisons should be made with the newest colonoscopes which are less stiff.
Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study)
Authors: PM Rothwell, AJ Coull, LE Silver, JF Fairhead, MF Giles, CE Lovelock, JNE Redgrave, LM Bull, SJV Welch, FC Cuthbertson, LE Binney, SA Gutnikov, P Anslow, AP Banning, D Mant, Z Mehta
Journal: The Lancet (2005)
Associations between pre-employment immunologic and airway mucosal factors and the development of occupational allergy
Authors: Esmeralda J.M. Krop, Dick J.J. Heederik, René Lutter, Gea de Meer, Rob C. Aalberse, Henk M. Jansen, Jaring S. van der Zee
Journal: Journal of Allergy and Clinical Immunology (2009)
Racial and Center Differences in Hemodialysis Adequacy in Children Treated at Pediatric Centers
Authors: Mary B. Leonard, Donald M. Stablein, Martin Ho, Kathy Jabs, Harold I. Feldman
Journal: Journal of the American Society of Nephrology (2004)

This study assessed hemodialysis adequacy in pediatric centers. Monthly adequacy data were requested in NAPRTCS enrollees on hemodialysis for at least 6 mo. Data forms were returned for 147 children from 32 centers. Data are presented for the 138 children (57% boys, 45% black) that were dialyzed 3 times/wk, representing 2282 patient-months of follow-up. Pre- and postdialysis BUN levels were reported in all children. Kt/V values were reported in 76 children; however, sufficient data were obtained to calculate Kt/V in 129 children. On average, 14.9 Kt/V and 15.2 urea reduction ratio (URR) values were calculated per child. Aggregate dialysis dose was defined as adequate if Kt/V was >1.2 in at least 75% of calculated Kt/V measures within a subject. Mean +/- SD age was 11.3 +/- 3.7 yr (median, 12.0 yr). Hemodialysis dose was variable within subjects (median CV%: URR 8.2, Kt/V 16.9). Aggregate dialysis dose was adequate in 70% of subjects. Multivariate logistic regression showed male gender (OR, 0.41; 95% CI, 0.16 to 0.98), black race (OR, 0.28; 95% CI, 0.11 to 0.67), larger body surface area (fourth versus first quartile: OR, 0.22; 95% CI, 0.05 to 0.80), and absence of reported Kt/V at the treating center (OR, 0.26; 95% CI, 0.10 to 0.62) were significant predictors of inadequate dialysis dose. Age, renal diagnosis, and center size were not associated with adequacy. Racial and gender disparities in hemodialysis dose existed among children at specialized academic pediatric centers and a substantial proportion received inadequate hemodialysis.
Partial Thrombosis of the False Lumen in Patients with Acute Type B Aortic Dissection
Authors: Thomas T. Tsai, Arturo Evangelista, Christoph A. Nienaber, Truls Myrmel, Gabriel Meinhardt, Jeanna V. Cooper, Dean E. Smith, Toru Suzuki, Rossella Fattori, Alfredo Llovet, James Froehlich, Stuart Hutchison, Alessandro Distante, Thoralf Sundt, Joshua Beckman, James L. Januzzi, Eric M. Isselbacher, Kim A. Eagle
Journal: New England Journal of Medicine (2007)

Patency or thrombosis of the false lumen in type B acute aortic dissection has been found to predict outcomes. The prognostic implications of partial thrombosis of the false lumen have not yet been elucidated.We examined 201 patients with type B acute aortic dissection who were enrolled in the International Registry of Acute Aortic Dissection between 1996 and 2003 and who survived to hospital discharge. Kaplan-Meier mortality curves were stratified according to the status of the false lumen (patent, partial thrombosis, or complete thrombosis) as determined during the index hospitalization. Cox proportional-hazards analysis was performed to identify independent predictors of death.During the index hospitalization, 114 patients (56.7%) had a patent false lumen, 68 patients (33.8%) had partial thrombosis of the false lumen, and 19 (9.5%) had complete thrombosis of the false lumen. The mean (+/-SD) 3-year mortality rate for patients with a patent false lumen was 13.7+/-7.1%, for those with partial thrombosis was 31.6+/-12.4%, and for those with complete thrombosis was 22.6+/-22.6% (median follow-up, 2.8 years; P=0.003 by the log-rank test). Independent predictors of postdischarge mortality were partial thrombosis of the false lumen (relative risk, 2.69; 95% confidence interval [CI], 1.45 to 4.98; P=0.002), a history of aortic aneurysm (relative risk, 2.05; 95% CI, 1.07 to 3.93; P=0.03), and a history of atherosclerosis (relative risk, 1.87; 95% CI, 1.01 to 3.47; P=0.05).Mortality is high after discharge from the hospital among patients with type B acute aortic dissection. Partial thrombosis of the false lumen, as compared with complete patency, is a significant independent predictor of postdischarge mortality in these patients.
Human Leukocyte/Endothelial Cell Interactions and Mitochondrial Dysfunction in Type 2 Diabetic Patients and Their Association With Silent Myocardial Ischemia
Authors: Antonio Hernandez-Mijares, Milagros Rocha, Susana Rovira-Llopis, Celia Bañuls, Lorena Bellod, Carmen de Pablo, Angeles Alvarez, Ildefonso Roldan-Torres, Eva Sola-Izquierdo, Victor M. Victor
Journal: Diabetes Care (2013)

OBJECTIVE Diabetes is associated with oxidative stress and increased mortality, but a possible correlation between leukocyte-endothelium interactions, oxidative stress, and silent myocardial ischemia (SMI) is yet to be confirmed. RESEARCH DESIGN AND METHODS Mitochondrial dysfunction and interactions between leukocytes and human umbilical vein endothelial cells were evaluated in 200 type 2 diabetic patients (25 with SMI) and 60 body composition– and age-matched control subjects. A possible correlation between these parameters and the onset of SMI was explored, and anthropometric and metabolic parameters were also analyzed. RESULTS Waist, levels of triglycerides, proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α), HbA1c, high-sensitivity C-reactive protein (hs-CRP), glucose, and insulin, and homeostasis model assessment of insulin resistance were higher in diabetic patients than in control subjects. However, no statistical differences in hs-CRP and insulin levels were detected when the data were adjusted for waist. None of these parameters varied between SMI and non-SMI patients. Mitochondrial function was impaired and leukocyte-endothelium interactions were more frequent among diabetic patients, which was evident in the lower mitochondrial O2 consumption, membrane potential, polymorphonuclear cell rolling velocity, and GSH/GSSG ratio, and in the higher mitochondrial reactive oxygen species production and rolling flux, adhesion, and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin molecules observed in these subjects. Moreover, these differences correlated with SMI. Statistical differences were maintained after adjusting the data for BMI and waist, with the exception of VCAM-1 levels when adjusted for waist. CONCLUSIONS Oxidative stress, mitochondrial dysfunction, and endothelium-inducing leukocyte-endothelium interactions are features of type 2 diabetes and correlate with SMI.
Lactic Acidosis Update for Critical Care Clinicians
Authors: FRIEDRICH C. LUFT
Journal: Journal of the American Society of Nephrology (2001)

Lactic acidosis is a broad-anion gap metabolic acidosis caused by lactic acid overproduction or underutilization. The quantitative dimensions of these two mechanisms commonly differ by 1 order of magnitude. Overproduction of lactic acid, also termed type A lactic acidosis, occurs when the body must regenerate ATP without oxygen (tissue hypoxia). Circulatory, pulmonary, or hemoglobin transfer disorders are commonly responsible. Overproduction of lactate also occurs with cyanide poisoning or certain malignancies. Underutilization involves removal of lactic acid by oxidation or conversion to glucose. Liver disease, inhibition of gluconeogenesis, pyruvate dehydrogenase (thiamine) deficiency, and uncoupling of oxidative phosphorylation are the most common causes. The kidneys also contribute to lactate removal. Concerns have been raised regarding the role of metformin in the production of lactic acidosis, on the basis of individual case reports. The risk appears to be considerably less than with phenformin and involves patients with underlying severe renal and cardiac dysfunction. Drugs used to treat lactic acidosis can aggravate the condition. NaHCO(3) increases lactate production. Treatment of type A lactic acidosis is particularly unsatisfactory. NaHCO(3) is of little value. Carbicarb is a mixture of Na(2)CO(3) and NaHCO(3) that buffers similarly to NaHCO(3) but without net generation of CO(2). The results from animal studies are promising; however, clinical trials are sparse. Dichloroacetate stimulates pyruvate dehydrogenase and improves laboratory values, but unfortunately not survival rates, among patients with lactic acidosis. Hemofiltration has been advocated for the treatment of lactic acidosis, on the basis of anecdotal experiences. However, kinetic studies of lactate removal do not suggest that removal can counteract lactate production in any meaningful way. The ideal treatment is to stop acid production by treating the underlying disorder.
The Troponin C G159D Mutation Blunts Myofilament Desensitization Induced by Troponin I Ser23/24 Phosphorylation
Authors: Brandon J. Biesiadecki, Tomoyoshi Kobayashi, John S. Walker, R. John Solaro, Pieter P. de Tombe
Journal: Circulation Research (2007)

Striated muscle contraction is regulated by the binding of Ca 2+ to the N-terminal regulatory lobe of the cardiac troponin C (cTnC) subunit in the troponin complex. In the heart, β-adrenergic stimulation induces protein kinase A phosphorylation of cardiac troponin I (cTnI) at Ser23/24 to alter the interaction of cTnI with cTnC in the troponin complex and is critical to the regulation of cardiac contractility. We investigated the effect of the dilated cardiomyopathy linked cTnC Gly159 to Asp (cTnC-G159D) mutation on the development of Ca 2+ -dependent tension and ATPase rate in whole troponin-exchanged skinned rat trabeculae. Even though this mutation is located in the C-terminal lobe of cTnC, the G159D mutation was demonstrated to depress ATPase activation and filament sliding in vitro. The effects of this mutation within the cardiac myofilament are unknown. Our results demonstrate that the cTnC-G159D mutation by itself does not alter the myofilament response to Ca 2+ in the cardiac muscle lattice. However, in the presence of cTnI phosphorylated at Ser23/24, which reduced Ca 2+ sensitivity and enhanced cross-bridge cycling in controls, cTnC-G159D specifically blunted the phosphorylation induced decrease in Ca 2+ -sensitive tension development without altering cross-bridge cycling. Measurements in purified troponin confirmed that this cTnC-G159D blunting of myofilament desensitization results from altered Ca 2+ -binding to cTnC. Our results provide novel evidence that modification of the cTnC-cTnI interaction has distinct effects on troponin Ca 2+ -binding and cross-bridge kinetics to suggest a novel role for thin filament mutations in the modulation of myofilament function through β-adrenergic signaling as well as the development of cardiomyopathy.
Physical Function Limitations Among Middle-Aged and Older Adults With Prediabetes
Authors: Pearl G. Lee, Christine T. Cigolle, Jinkyung Ha, Lillian Min, Susan L. Murphy, Caroline S. Blaum, William H. Herman
Journal: Diabetes Care (2013)

OBJECTIVE To describe the prevalence of physical function limitations among a nationally representative sample of adults with prediabetes. RESEARCH DESIGN AND METHODS We performed a cross-sectional analysis of 5,991 respondents ≥53 years of age from the 2006 wave of the Health and Retirement Study. All respondents self-reported physical function limitations and comorbidities (chronic diseases and geriatric conditions). Respondents with prediabetes reported no diabetes and had a measured glycosylated hemoglobin (HbA1c) of 5.7–6.4%. Descriptive analyses and logistic regressions were used to compare respondents with prediabetes versus diabetes (diabetes history or HbA1c ≥6.5%) or normoglycemia (no diabetes history and HbA1c &amp;lt;5.7%). RESULTS Twenty-eight percent of respondents ≥53 years of age had prediabetes; 32% had mobility limitations (walking several blocks and/or climbing a flight of stairs); 56% had lower-extremity limitations (getting up from a chair and/or stooping, kneeling, or crouching); and 33% had upper-extremity limitations (pushing or pulling heavy objects and/or lifting &amp;gt;10 lb). Respondents with diabetes had the highest prevalence of comorbidities and physical function limitations, followed by those with prediabetes, and then normoglycemia (P &amp;lt; 0.05). Compared with respondents with normoglycemia, respondents with prediabetes had a higher odds of having functional limitations that affected mobility (odds ratio [OR] 1.48), the lower extremities (OR 1.35), and the upper extremities (OR 1.37) (all P &amp;lt; 0.01). The higher odds of having lower-extremity limitations remained after adjusting for age, sex, and body mass index (OR 1.21, P &amp;lt; 0.05). CONCLUSIONS Comorbidities and physical function limitations are prevalent among middle-aged and older adults with prediabetes. Effective lifestyle interventions to prevent diabetes must accommodate physical function limitations.
CDK1 Phosphorylation of YAP Promotes Mitotic Defects and Cell Motility and Is Essential for Neoplastic Transformation
Authors: Shuping Yang, Lin Zhang, Miao Liu, Rong Chong, Shi-Jian Ding, Yuanhong Chen, Jixin Dong
Journal: Cancer Research (2013)

Abstract The Yes-associated protein, YAP, is a downstream effector of the Hippo pathway of cell-cycle control that plays important roles in tumorigenesis. Hippo-mediated phosphorylation YAP, mainly at S127, inactivates YAP function. In this study, we define a mechanism for positive regulation of YAP activity that is critical for its oncogenic function. Specifically, we found that YAP is phosphorylated in vitro and in vivo by the cell-cycle kinase CDK1 at T119, S289, and S367 during the G2–M phase of the cell cycle. We also found that ectopic expression of a phosphomimetic YAP mutant (YAP3D, harboring T119D/S289D/S367D) was sufficient to induce mitotic defects in immortalized epithelial cells, including centrosome amplification, multipolar spindles, and chromosome missegregation. Finally, we documented that mitotic phosphorylation of YAP was sufficient to promote cell migration and invasion in a manner essential for neoplastic cell transformation. In support of our findings, CDK1 inhibitors largely suppressed cell motility mediated by activated YAP-S127A but not the phosphomimetic mutant YAP3D. Collectively, our results reveal a previously unrecognized mechanism for controlling the activity of YAP that is crucial for its oncogenic function mediated by mitotic dysregulation. Cancer Res; 73(22); 6722–33. ©2013 AACR.
Assessment of the clinical significance of gelatinase activity in patients with juvenile idiopathic arthritis using quantitative protein substrate zymography
Authors: Nick J Peake, Helen E Foster, Khulood Khawaja, Tim E Cawston, Andrew D Rowan
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To measure gelatinase activities in paired synovial fluid (SF) and serum of patients with juvenile idiopathic arthritis (JIA), and to assess how these activities relate to clinical and laboratory measures of disease activity. <b>Methods:</b> A quantitative protein substrate zymography method was adapted and validated for use with serum and SF. Bands of activity were measured by densitometry and correlated with standard laboratory indicators of inflammation: erythrocyte sedimentation rate and platelet count. <b>Results:</b> Gelatinase activity was found consistently in patients with JIA, with reproducible, quantified bands of activity corresponding to pro-matrix metalloproteinase-9 (pro-MMP-9), including the neutrophil associated lipocalin complex, and pro- and active forms of MMP-2. Both active MMP-2 and pro-MMP-9 were higher in JIA serum than in controls, though no differences were seen between patients grouped according to age, disease duration, or JIA subtype. However, SF MMP-9 correlated significantly with the laboratory indicators of inflammation, as did the relative level of active MMP-2. <b>Conclusions:</b> Both MMP-2 and MMP-9 gelatinolytic activities are raised during active JIA and associated with inflammatory activity regardless of age and disease duration, supporting a role for MMPs in the breakdown of joint components from early in disease. These MMPs may be specific markers of active joint destruction linked to inflammatory JIA, MMP-9 as a product of infiltrating cells, and the activation of MMP-2 produced within the joint.
Lung mechanics and activity of slowly adapting airway stretch receptors
Authors: FB Sant'Ambrogio, G Sant'Ambrogio, JT Fisher
Journal: European Respiratory Journal (1988)

Transpulmonary pressure is thought to be closely associated with slowly adapting mechanoreceptor activity. The transpulmonary pressure required to inflate the lung to a given volume depends on pulmonary compliance: for equal tidal volumes less pressure will be required if compliance is higher. Therefore, an inverse relationship is expected between receptor activity and lung compliance for equal changes in lung volume. We have studied 33 slowly adapting airway stretch receptors (SARs) in anaesthetized, vagotomized, paralysed and artificially ventilated dogs, with the chest open, at constant tidal volume and frequency. After lung compliance had been increased by hyperinflation, all of the ten tracheal receptors studied and fourteen of the 23 intrapulmonary receptors reduced their activity. Of the remaining intrapulmonary receptors five increased their activity and four were unaffected. Our results indicate that, although airway stretch receptor discharge is usually related to transpulmonary pressure, this relationship is not always present in the case of peripherally located endings; this is possibly due to a discrepancy between local transmural pressure and overall transpulmonary pressure. Thus, in addition to the well described independence of SAR discharge frequency from lung volume, the activity of SARs having peripheral locations is not always predictable on the basis of changes in transpulmonary pressure.