tbuckley/cabot-search huggingface dataset:
Effect of Weight Loss on LDL and HDL Kinetics in the Metabolic Syndrome
Authors: Theodore W.K. Ng, Gerald F. Watts, P. Hugh R. Barrett, Kerry-Anne Rye, Dick C. Chan
Journal: Diabetes Care (2007)

The purpose of this study was to examine the effect of weight loss on LDL and HDL kinetics and plasma retinol-binding protein-4 (RBP-4) and adiponectin levels in men with the metabolic syndrome.LDL apolipoprotein (apo)B-100 and HDL apoA-I kinetics were studied in 35 obese men with the metabolic syndrome at the start and end of a 16-week intervention trial of a hypocaloric, low-fat diet (n = 20) versus a weight maintenance diet (n = 15) using a stable isotope technique and multicompartmental modeling.Consumption of the low-fat diet produced significant reductions (P < 0.01) in BMI, abdominal fat compartments, and homeostasis model assessment score compared with weight maintenance. These were associated with a significant increase in adiponectin and a fall in plasma RBP-4, triglycerides, LDL cholesterol, and LDL apoB-100 concentration (P < 0.05). Weight loss significantly increased the catabolism of LDL apoB-100 (+27%, P < 0.05) but did not affect production; it also decreased both the catabolic (-13%) and production (-13%) rates of HDL apoA-I (P < 0.05), thereby not altering plasma HDL apoA-I or HDL cholesterol concentrations. VLDL apoB-100 production fell significantly with weight loss (P < 0.05). The increase in LDL catabolism was inversely correlated with the fall in RBP-4 (r = -0.54, P < 0.05) and the decrease in HDL catabolism with the rise in adiponectin (r = -0.56, P < 0.01).In obese men with metabolic syndrome, weight loss with a low-fat diet decreases the plasma LDL apoB-100 concentration by increasing the catabolism of LDL apoB-100; weight loss also delays the catabolism of HDL apoA-I with a concomitant reduction in the secretion of HDL apoA-I. These effects of weight loss could partly involve changes in RBP-4 and adiponectin levels.
Women’s emotional adjustment to IVF: a systematic review of 25 years of research
Authors: C.M. Verhaak, J.M.J. Smeenk, A.W.M. Evers, J.A.M. Kremer, F.W. Kraaimaat, D.D.M. Braat
Journal: Human Reproduction Update (2006)

This review provides an overview of how women adjust emotionally to the various phases of IVF treatment in terms of anxiety, depression or general distress before, during and after different treatment cycles. A systematic scrutiny of the literature yielded 706 articles that paid attention to emotional aspects of IVF treatment of which 27 investigated the women's emotional adjustment with standardized measures in relation to norm or control groups. Most studies involved concurrent comparisons between women in different treatment phases and different types of control groups. The findings indicated that women starting IVF were only slightly different emotionally from the norm groups. Unsuccessful treatment raised the women's levels of negative emotions, which continued after consecutive unsuccessful cycles. In general, most women proved to adjust well to unsuccessful IVF, although a considerable group showed subclinical emotional problems. When IVF resulted in pregnancy, the negative emotions disappeared, indicating that treatment-induced stress is considerably related to threats of failure. The concurrent research reviewed, should now be underpinned by longitudinal studies to provide more information about women's long-term emotional adjustment to unsuccessful IVF and about indicators of risk factors for problematic emotional adjustment after unsuccessful treatment, to foster focused psychological support for women at risk.
Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis
Authors: P. E. Ronksley, S. E. Brien, B. J. Turner, K. J. Mukamal, W. A. Ghali
Journal: BMJ (2011)

Objective To conduct a comprehensive systematic review and meta-analysis of studies assessing the effect of alcohol consumption on multiple cardiovascular outcomes. Design Systematic review and meta-analysis. Data sources A search of Medline (1950 through September 2009) and Embase (1980 through September 2009) supplemented by manual searches of bibliographies and conference proceedings. Inclusion criteria Prospective cohort studies on the association between alcohol consumption and overall mortality from cardiovascular disease, incidence of and mortality from coronary heart disease, and incidence of and mortality from stroke. Studies reviewed Of 4235 studies reviewed for eligibility, quality, and data extraction, 84 were included in the final analysis. Results The pooled adjusted relative risks for alcohol drinkers relative to non-drinkers in random effects models for the outcomes of interest were 0.75 (95% confidence interval 0.70 to 0.80) for cardiovascular disease mortality (21 studies), 0.71 (0.66 to 0.77) for incident coronary heart disease (29 studies), 0.75 (0.68 to 0.81) for coronary heart disease mortality (31 studies), 0.98 (0.91 to 1.06) for incident stroke (17 studies), and 1.06 (0.91 to 1.23) for stroke mortality (10 studies). Dose-response analysis revealed that the lowest risk of coronary heart disease mortality occurred with 1–2 drinks a day, but for stroke mortality it occurred with ≤1 drink per day. Secondary analysis of mortality from all causes showed lower risk for drinkers compared with non-drinkers (relative risk 0.87 (0.83 to 0.92)). Conclusions Light to moderate alcohol consumption is associated with a reduced risk of multiple cardiovascular outcomes.
MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival
Authors: Younghwa Kim, Ping Zhou, Liping Qian, Jen-Zen Chuang, Jessica Lee, Chenjian Li, Costantino Iadecola, Carl Nathan, Aihao Ding
Journal: The Journal of Experimental Medicine (2007)

The innate immune system relies on evolutionally conserved Toll-like receptors (TLRs) to recognize diverse microbial molecular structures. Most TLRs depend on a family of adaptor proteins termed MyD88s to transduce their signals. Critical roles of MyD88-1-4 in host defense were demonstrated by defective immune responses in knockout mice. In contrast, the sites of expression and functions of vertebrate MyD88-5 have remained elusive. We show that MyD88-5 is distinct from other MyD88s in that MyD88-5 is preferentially expressed in neurons, colocalizes in part with mitochondria and JNK3, and regulates neuronal death. We prepared MyD88-5/GFP transgenic mice via a bacterial artificial chromosome to preserve its endogenous expression pattern. MyD88-5/GFP was detected chiefly in the brain, where it associated with punctate structures within neurons and copurified in part with mitochondria. In vitro, MyD88-5 co-immunoprecipitated with JNK3 and recruited JNK3 from cytosol to mitochondria. Hippocampal neurons from MyD88-5-deficient mice were protected from death after deprivation of oxygen and glucose. In contrast, MyD88-5-null macrophages behaved like wild-type cells in their response to microbial products. Thus, MyD88-5 appears unique among MyD88s in functioning to mediate stress-induced neuronal toxicity.
Clonal deletion of self-reactive T cells in irradiation bone marrow chimeras and neonatally tolerant mice. Evidence for intercellular transfer of Mlsa.
Authors: D E Speiser, R Schneider, H Hengartner, H R MacDonald, R M Zinkernagel
Journal: The Journal of Experimental Medicine (1989)

Tolerance to Mlsa has been shown to be associated with clonal deletion of cells carrying TCR beta chain variable regions V beta 6 or V beta 8.1 in mice possessing I-E antigens. To evaluate the rules of tolerance induction to Mlsa we prepared irradiation bone marrow chimeras expressing Mlsa or Mlsb and I-E by different cell types. Deletion of V beta 6+, Mlsa-reactive T cells required the presence of Mlsa and I-E products either on bone marrow-derived cells or on irradiated recipient cells. Tolerance was induced when Mlsa and I-E were expressed by distinct cells of the chimera. Also neonatally tolerized mice exhibited depletion of V beta 6+ cells after injection of I-E- Mlsa spleen cells (DBA/1) into newborn I-E+ Mlsb mice (BALB/c x B10.G)F1. These results suggest that the product of the Mlsa locus is soluble and/or may be transferred from cell to cell and bound to I-E antigens. The chimera experiments also showed that tolerance to Mlsa is H-2 allele independent, i.e., is apparently unrestricted. Differentiation of chimeric (H-2d/Mlsa x H-2q/Mlsb)F1 stem cells in either an H-2d or an H-2q thymus revealed that tolerance assessed by absence of V beta 6+ T cells is not dependent on the thymically determined restriction specificity of T cells.
Calculation of coronary vascular resistance
Authors: R. F BELLAMY
Journal: Cardiovascular Research (1980)

A conscious, chronically instrumented canine model was used to investigate resistance changes in the distribution of the circumflex coronary artery as the artery was constricted. Several discrete constrictions were studied at two different levels of flow: resting and peak flow reactive hyperaemia. The resistance of the bed downstream from the constriction was calculated by formulae which defined the coronary back pressure as either venous pressure (Pv) or the arterial pressure at which coronary flow ceased (Pc). When Pv was taken as the back pressure, the resistance of the coronary bed during reactive hyperaemia progressively increased as the upstream artery was constricted. When Pc was taken as the back pressure, calculated coronary resistance for reactive hyperaemia showed little change. It is not known if elastic recoil of coronary resistance vessels, consequent to low poststenotic pressure, could occur to the extent required to be the physical basis for the calculated increase in resistance when Pv is taken to be the back pressure. Use of Pc as the back pressure implies that the coronary circulation contains a segment having the hydraulic characteristics of a collapsible tube.
Respiration during sleep in kyphoscoliosis.
Authors: E H Sawicka, M A Branthwaite
Journal: Thorax (1987)

Eleven subjects with non-paralytic and 10 with paralytic kyphoscoliosis and nine normal control subjects were studied during sleep. The Cobb angle of those with kyphoscoliosis varied from 60 degrees to 140 degrees (median 100 degrees) and the vital capacity varied from 17% to 56% (median 28%) of the value predicted on the basis of span. Recordings made during sleep included expired carbon dioxide tension at the nose, gas flow at the mouth, arterial oxygen saturation, chest wall movement, and the electroencephalogram, electro-oculogram, and electrocardiogram. In three subjects transcutaneous carbon dioxide tension was measured simultaneously. Patients with kyphoscoliosis hypoventilated during sleep, particularly in rapid eye movement sleep, resulting in a rise in end tidal and transcutaneous carbon dioxide tension, and a reduction in oxygen saturation to a degree not observed in normal subjects. Reduced chest wall movement was the major cause of these episodes, which were more frequent and occupied a greater proportion of sleep time in those with kyphoscoliosis than in normal subjects. Serious cardiac arrhythmias were rarely associated. It is concluded that disturbances of respiration during sleep occur in patients with kyphoscoliosis and that these may be important in the pathogenesis of cardiorespiratory failure.
Macrophage oxygen-dependent antimicrobial activity. I. Susceptibility of Toxoplasma gondii to oxygen intermediates.
Authors: H W Murray, Z A Cohn
Journal: The Journal of Experimental Medicine (1979)

A sensitive method for evaluating extracellular parasite viability was used to determine the in vitro susceptibility of virulent Toxoplasma gondii to selected oxygen intermediates. By acridine orange fluorescent staining criteria, toxoplasmas were resistant to up to either 10(-3) M reagent H2O2 or H2O2 generated by glucose-glucose oxidase. In keeping with a lack of sensitivity to H2O2, toxoplasmas contained endogenous catalase (5.7 x 10(-4) Baudhuin units/10(6) organisms). The addition of a peroxidase and halide, however, markedly accelerated killing and lowered the H2O2 requirement by 1,000-fold. In contrast, toxoplasmas were promptly killed after exposure to products generated by xanthine (1.5 x 10(-4) M) and xanthine oxidase (50 micrograms). The inhibition of this system's microbicidal activity by scavengers of O2- (superoxide dismutase) and H2O2 (catalase) indicated that although neither O2- nor H2O2 were toxoplasmacidal, their interaction was required for parasite killing. Quenching OH. and 1O2, presumed products of O2--H2O2 interaction, by mannitol, benzoate, diazabicyclooctane, and histidine, also inhibited toxoplasma killing by xanthine-xanthine oxidase. These findings suggested that O2- and H2O2 functioned in precursor roles and that OH. and 1O2 were toxoplasmacidal. The capacity of normal peritoneal macrophages to pinocytose an oxygen intermediate scavenger, soluble catalase, was also demonstrated. Appreciable extraphagosomal concentrations of catalase were achieved by exposing macrophages to 1 mg/ml of the enzyme for 3 h. Maintenance of high intracellular levels required constant exposure because interiorized catalase was rapidly degraded.
A Randomized Trial Comparing Defined-Duration With Continuous Irinotecan Until Disease Progression in Fluoropyrimidine and Thymidylate Synthase Inhibitor—Resistant Advanced Colorectal Cancer
Authors: Rohit Lal, James Dickson, David Cunningham, Ian Chau, Andrew R. Norman, Paul J. Ross, Clare Topham, Gary Middleton, Mark Hill, Jacqui Oates
Journal: Journal of Clinical Oncology (2004)

Irinotecan given until disease progression is an accepted standard treatment for advanced colorectal cancer (CRC) resistant to fluoropyrimidines. It is not known whether a predefined period of irinotecan treatment would result in similar duration of disease control. We performed a multicenter phase III trial to compare the two policies of defined-duration versus continuous irinotecan treatment.Three hundred thirty-three eligible patients with advanced CRC progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered. After receiving eight cycles of irinotecan given at 350 mg/m2 once every 3 weeks, 55 patients with responding or stable disease were randomly assigned to stop irinotecan (n = 30) or continue until disease progression (n = 25). Registered patients were not randomly assigned predominantly due to disease progression (n = 236) and intolerable toxicity (n = 38).From the time of random assignment, there were no differences in failure-free survival (P = .999) or overall survival (P = .11) between the two arms. No difference was seen in mean global health status quality-of-life score between the two arms at 12 weeks after random assignment. No grade 3 diarrhea and febrile neutropenia was seen in the continue-irinotecan arm after random assignment.For most patients, the decision to continue on irinotecan beyond 24 weeks is influenced by disease progression or treatment-related toxicity. However, for 17% of patients in whom this decision is clinically relevant, there seems to be little benefit from continuing irinotecan, though the drug was well tolerated without any deterioration in quality of life.
Neurovascular disturbances after implant surgery
Authors: Reinhilde Jacobs, Marc Quirynen, Michael M. Bornstein
Journal: Periodontology 2000 (2014)

Abstract With a steadily increasing impact of oral implant placement in daily practice, the number of reported surgical complications has also been growing. Recent studies reveal significant variation in the occurrence and morphology of neurovascular canal structures in the jaw bone. All those structures contain a neurovascular bundle, the diameter of which may be large enough to cause clinically significant damage. Therefore, it has become obvious that presurgical radiographic planning of jaw‐bone surgery should pay attention to the neurovascular structures and their likely variations, in addition to examining many other factors, such as jaw‐bone morphology and volume, bone trabecular structure and the absence of bone or tooth pathology. A critical review is accomplished to explore the potential risks for neurovascular complications after implant placement, with evidence derived from histologic, anatomic, clinical and radiologic studies. In this respect, cross‐sectional imaging can often be advocated, as it is obvious that the inherent three‐dimensional nature of jaw‐bone anatomy may clearly benefit from a detailed spatial image analysis. Although this could initially be realized by conventional computed tomography, in current practice, dentomaxillofacial cone beam computed tomography might be used, as it offers high‐quality images at low radiation dose levels and costs.
Outcome of High-Risk Stage IC, Grade 3, Compared With Stage I Endometrial Carcinoma Patients: The Postoperative Radiation Therapy in Endometrial Carcinoma Trial
Authors: Carien L. Creutzberg, Wim L.J. van Putten, Carla C. Wárlám-Rodenhuis, Alfons C.M. van den Bergh, Karin A.J. De Winter, Peter C.M. Koper, Marnix L.M. Lybeert, Annerie Slot, Ludy C.H.W. Lutgens, Marika C. Stenfert Kroese, Henk Beerman, Mat van Lent
Journal: Journal of Clinical Oncology (2004)

Stage IC, grade 3 endometrial cancer is regarded as a high-risk category. Stage IC, grade 3 patients were not eligible for the randomized Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial, but were registered and received postoperative radiotherapy.The PORTEC trial included 715 patients with stage IC, grade 1 or 2, and stage IB, grade 2 or 3 endometrial cancer. Patients were randomly assigned after surgery to receive pelvic radiotherapy (RT) or no further treatment. A total of 104 patients with stage IC, grade 3 endometrial cancer were registered, of whom 99 could be evaluated. Patterns of relapse and survival were compared with PORTEC patients receiving RT. Median follow-up was 83 months.The actuarial 5-year rates of locoregional relapse were 1% to 3% for PORTEC patients who received RT, compared with 14% for stage IC, grade 3 patients. Five-year distant metastases rates were 3% to 8% for grade 1 and 2 tumors; 20% for stage IB, grade 3 tumors; and 31% for stage IC, grade 3 tumors. Overall survival rates were 83% to 85% for grades 1 and 2; 74% for stage IB, grade 3; and 58% for stage IC, grade 3 patients (P <.001). In multivariate analysis grade 3 was the most important adverse prognostic factor for relapse and death as a result of endometrial cancer (hazard ratios, 5.4 and 5.5; P <.0001).Patients with stage IC, grade 3 endometrial carcinoma are at high risk of early distant spread and endometrial carcinoma-related death. Novel strategies for adjuvant therapy should be explored to improve survival for this patient group.
Sugar Absorption in the Intestine: The Role of GLUT2
Authors: George L. Kellett, Edith Brot-Laroche, Oliver J. Mace, Armelle Leturque
Journal: Annual Review of Nutrition (2008)

Intestinal glucose absorption comprises two components. One is classical active absorption mediated by the Na+/glucose cotransporter. The other is a diffusive component, formerly attributed to paracellular flow. Recent evidence, however, indicates that the diffusive component is mediated by the transient insertion of glucose transporter type 2 (GLUT2) into the apical membrane. This apical GLUT2 pathway of intestinal sugar absorption is present in species from insect to human, providing a major route at high sugar concentrations. The pathway is regulated by rapid trafficking of GLUT2 to the apical membrane induced by glucose during assimilation of a meal. Apical GLUT2 is therefore a target for multiple short-term and long-term nutrient-sensing mechanisms. These include regulation by a newly recognized pathway of calcium absorption through the nonclassical neuroendocrine l-type channel Cav1.3 operating during digestion, activation of intestinal sweet taste receptors by natural sugars and artificial sweeteners, paracrine and endocrine hormones, especially insulin and GLP-2, and stress. Permanent apical GLUT2, resulting in increased sugar absorption, is a characteristic of experimental diabetes and of insulin-resistant states induced by fructose and fat. The nutritional consequences of apical and basolateral GLUT2 regulation are discussed in the context of Western diet, processed foods containing artificial sweeteners, obesity, and diabetes.
Pharmacogenetic Risk Factors for Osteonecrosis of the Hip Among Children With Leukemia
Authors: Mary V. Relling, Wenjian Yang, Soma Das, Edwin H. Cook, Gary L. Rosner, Michael Neel, Scott Howard, Raul Ribeiro, John T. Sandlund, Ching-Hon Pui, Sue C. Kaste
Journal: Journal of Clinical Oncology (2004)

One of the adverse effects of therapy for acute lymphoblastic leukemia (ALL) is osteonecrosis of the hip. Putative risk factors for osteonecrosis have included being female, white race, and older age. Our goal was to define possible genetic risk factors for osteonecrosis among children treated for newly diagnosed ALL.Using a candidate gene approach, we determined the genotypes for 16 common polymorphisms in genes likely to affect the pharmacokinetics or pharmacodynamics of antileukemic medications in 64 children with ALL. Therapy included glucocorticoids and antifolates. Magnetic resonance imaging of both hips was used to diagnose osteonecrosis, and was performed at similar times from the start of ALL therapy (P =.61) in the 25 patients with and the 39 patients without osteonecrosis (median, 447 days and 443 days, respectively).In addition to age older than 10 years (odds ratio [OR], 24.2; P =.0001) and white race (OR, 11.1; P =.037), host factors for osteonecrosis included the vitamin D receptor FokI start site CC genotype (OR, 4.5; P =.045), and the thymidylate synthase low activity 2/2 enhancer repeat genotype (OR, 7.4; P =.049).Because folate-related and vitamin D-receptor genetic variants have been associated with bone and vasculature morbidity, these pharmacogenetic associations likely reflect the interaction of antileukemic medications with germline sensitivity to drug actions, and might identify ALL patients at highest risk to develop osteonecrosis.
ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy
Authors: R Mullenbach
Journal: Gut (2005)

Intrahepatic cholestasis of pregnancy (ICP) affects approximately 0.7% of pregnancies in the UK and is associated with prematurity, fetal distress, and intrauterine death. Homozygous mutations in the ATP8B1 gene cause cholestasis with a normal serum gamma-glutamyl transpeptidase (gamma-GT), and have been reported in two forms of cholestasis: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC).To establish whether mutations in ATP8B1 are associated with ICP in British casesSixteen well phenotyped women with ICP without raised gamma-GT were selected for sequence analysis. Subsequently, 182 patients and 120 controls were examined for the presence of the variants detected.All coding exons were sequenced in 16 cases. Eight ICP cases, including two women carrying a mutation, were investigated using in vivo hepatic (31)P magnetic resonance spectroscopy (MRS) RESULTS: Two heterozygous ATP8B1 transitions (208G>A and 2599C>T) that resulted in amino acid substitutions were identified; 208G>A was identified in three cases. MRS revealed an increased phosphodiester signal (Mann-Whitney U test, p = 0.03) and a decreased phosphomonoester/phosphodiester ratio (p = 0.04) in ICP cases compared with controls.We were able to demonstrate ATP8B1 mutations in ICP. MRS studies suggest that susceptibility to ICP is associated with a relative rise in biliary phospholipid. These data also suggest that MRS may be used for non-invasive assessment of the liver and biliary constituents in cholestasis.