tbuckley/cabot-search huggingface dataset:
The metabolism of IgE in patients with immunodeficiency states and neoplastic conditions.
Authors: A Iio, W Strober, S Broder, S H Polmar
Journal: Journal of Clinical Investigation (1977)

Serum IgE concentrations were determined and IgE turnover studies were performed in control individuals as well as in patients with several disease states. Patients with common variable hypogammaglobulinemia, thymoma and hypogammaglobulinemia, ataxia telangiectasia, and selective IgA deficiency had significantly decreased mean serum IgE concentrations. In turnover studies, this was found to be due to decreased IgE synthesis. In spite of these depressed mean values, some patients with common variable hypogammaglobulinemia had normal serum IgE concentrations and synthetic rates. Patients with the Wiskott-Aldrich syndrome had a significantly elevated mean serum IgE concentration. In one of four patients studied with the turnover technique, a strikingly high IgE concentration was present and was associated with an elevated IgE synthetic rate. Three other patients had both normal serum IgE concentrations and synthetic rates. Patients with chronic lymphocytic leukemia had significantly decreased mean serum concentrations and synthetic rates for IgE. The depressed IgE synthesis was associated with a significantly prolonged IgE half-life. Patients with Hodgkin's disease had significantly increased serum IgE concentrations. One of three patients studied had a high serum IgE concentration and synthetic rate of IgE. The two other patients had normal serum IgE concentrations associated with normal synthetic rates. Finally patients with protein-losing enteropathy or familial hypercatabolic hypoproteinemia had normal IgE concentrations associated with normal IgE metabolic parameters. In these cases, the disorder in the catabolic rate was not severe enough to affect the total amount of circulating IgE because IgE normally has a very high fractional catabolic rate. In general, IgE levels in a variety of disease states were correlated with IgE synthetic rates and abnormalities in the catabolic rate of IgE in disease did not exert an important effect on IgE concentration.
The Genomic Rate of Adaptive Amino Acid Substitution in Drosophila
Authors: Nicolas Bierne, Adam Eyre-Walker
Journal: Molecular Biology and Evolution (2004)

The proportion of amino acid substitutions driven by adaptive evolution can potentially be estimated from polymorphism and divergence data by an extension of the McDonald-Kreitman test. We have developed a maximum-likelihood method to do this and have applied our method to several data sets from three Drosophila species: D. melanogaster, D. simulans, and D. yakuba. The estimated number of adaptive substitutions per codon is not uniformly distributed among genes, but follows a leptokurtic distribution. However, the proportion of amino acid substitutions fixed by adaptive evolution seems to be remarkably constant across the genome (i.e., the proportion of amino acid substitutions that are adaptive appears to be the same in fast-evolving and slow-evolving genes; fast-evolving genes have higher numbers of both adaptive and neutral substitutions). Our estimates do not seem to be significantly biased by selection on synonymous codon use or by the assumption of independence among sites. Nevertheless, an accurate estimate is hampered by the existence of slightly deleterious mutations and variations in effective population size. The analysis of several Drosophila data sets suggests that approximately 25% +/- 20% of amino acid substitutions were driven by positive selection in the divergence between D. simulans and D. yakuba.
Metformin: A Therapeutic Opportunity in Breast Cancer
Authors: Ana M. Gonzalez-Angulo, Funda Meric-Bernstam
Journal: Clinical Cancer Research (2010)

Two important, related pathways are involved in cancer growth: the insulin/insulin-like growth factor-1 (IGF1) signaling pathway, which is activated when nutrients are available, and the adenosine mono-phosphate-activated protein kinase (AMPK) pathway, activated when cells are starved for carbohydrates. Metformin inhibits transcription of key gluconeogenesis genes in the liver, increases glucose uptake in skeletal muscle, and decreases circulating insulin levels. Metformin reduces levels of circulating glucose, increases insulin sensitivity, and reduces insulin resistance-associated hyperinsulinemia. At the level of cell signaling, metformin activates AMPK. There are extensive preclinical data showing the anticancer effects of metformin in all breast cancer subtypes as well as in cytotoxic therapy-resistant models. These data, and the epidemiological and retrospective data supporting the antineoplastic effects of metformin, provide the rationale to study the role of metformin for breast cancer therapy in a variety of clinical settings.
Disadvantage of Men Living Alone Participating in Radiation Therapy Oncology Group Head and Neck Trials
Authors: Andre A. Konski, Thomas F. Pajak, Benjamin Movsas, James Coyne, Jonathan Harris, Clement Gwede, Adam Garden, Sharon Spencer, Christopher Jones, Deborah Watkins-Bruner
Journal: Journal of Clinical Oncology (2006)

This study evaluated whether males without partners were disadvantaged for survival in Radiation Therapy Oncology Group (RTOG) head and neck cancer clinical trials.Patients treated on three RTOG trials were studied. The Cox proportional hazards model was used to determine if sex and the interaction between sex and marital/partner status were independent prognostic variables for overall survival controlling for Karnofsky performance status, tumor stage, nodal stage, primary site, and protocol treatment.A total of 1,901 patients (1,509 men) were entered onto the three RTOG trials, with 1,822 (1,438 men) analyzable patients. Prognostic variables independent of disease-related variables for survival in multivariate analyses restricted to men were age, marital/partner status, and income.The apparent disadvantage of unpartnered men is striking, even after controlling for disease and other demographic variables. Possible explanations could easily be tested in observational studies, leading to evaluation of simple interventions to improve their outcome.
Circulating 25-Hydroxyvitamin D Concentrations Are Correlated With Cardiometabolic Risk Among American Black and White Adolescents Living in a Year-Round Sunny Climate
Authors: Samip Parikh, De-huang Guo, Norman K. Pollock, Karen Petty, Jigar Bhagatwala, Bernard Gutin, Chris Houk, Haidong Zhu, Yanbin Dong
Journal: Diabetes Care (2012)

Low vitamin D status is common among healthy black and white adolescents residing at southern U.S. latitudes with a year-round sunny climate. Thus we aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk factors in this population.25(OH)D concentrations were measured with liquid chromatography tandem mass spectroscopy in 701 girls and boys (14-18 years old, 54% blacks, 49% females). Cardiometabolic risk was indexed by adipokines, inflammatory markers, fasting glucose, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and blood pressure (BP).Controlling for age, sex, race, sexual maturation, season, physical activity, and percent body fat, 25(OH)D concentrations were significantly correlated with adiponectin (r = 0.06, P = 0.05), leptin (r = -0.32, P < 0.01), fibrinogen (r = -0.05, P = 0.03), glucose (r = -0.16, P = 0.02), HOMA-IR (r = -0.17, P < 0.01), HDL cholesterol (r = 0.14, P = 0.02), systolic BP (r = -0.10, P = 0.02), and diastolic BP (r = -0.21, P < 0.01). When 25(OH)D concentrations were stratified into increasing tertiles, there were significant linear upward trends for adiponectin (P = 0.01) and HDL cholesterol (P = 0.04), but significant linear down trends for glucose (P < 0.01), HOMA-IR (P < 0.01), and systolic BP (P < 0.01), after adjusting for the above covariates.Circulating 25(OH)D concentrations are associated with various adverse cardiometabolic risk factors, independent of adiposity. Clinical trials addressing the effects of vitamin D supplementation on cardiometabolic risk are warranted in adolescents irrespective of their geographical regions.
THE COMMUNICATION OF SUICIDAL INTENT: A STUDY OF 134 CONSECUTIVE CASES OF SUCCESSFUL (COMPLETED) SUICIDE
Authors: ELI ROBINS, SEYMOUR GASSNER, JACK KAYES, ROBERT H. WILKINSON, GEORGE E. MURPHY
Journal: American Journal of Psychiatry (1959)

1. A study of the communication of suicidal ideas by 134 consecutive suicides has been done by means of systematic interviews with family, in-laws, friends, job associates, physicians, ministers, and others a short time after the suicide. 2. Two striking findings were that over two-thirds (69%) of the suicides had communicated suicidal ideas and that 41% had specifically stated they intended to commit suicide. In the majority of instances, the suicidal communications were of recent onset (months), repeatedly verbalized, and expressed to many persons. 3. Another striking finding was that 98% of these persons were probably clinically ill prior to their suicides. 4. The frequency of expression of suicidal ideas was not significantly related to age, sex, marital state, religion, whether living alone or not, clinical diagnosis, occupational status, income, or education. Chronic alcoholics had a somewhat greater tendency than the other diagnostic groups to make the specific statement that they intended to commit suicide. 5. The communication of suicidal ideas was analyzed as a general system of communication with reference to experimental psychological studies.
Engineering Design of Optimal Strategies for Blood Clot Dissolution
Authors: Scott L. Diamond
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract Blood clots form under hemodynamic conditions and can obstruct flow during angina, acute myocardial infarction, stroke, deep vein thrombosis, pulmonary embolism, peripheral thrombosis, or dialysis access graft thrombosis. Therapies to remove these clots through enzymatic and/or mechanical approaches require consideration of the biochemistry and structure of blood clots in conjunction with local transport phenomena. Because blood clots are porous objects exposed to local hemodynamic forces, pressure-driven interstitial permeation often controls drug penetration and the overall lysis rate of an occlusive thrombus. Reaction engineering and transport phenomena provide a framework to relate dosage of a given agent to potential outcomes. The design and testing of thrombolytic agents and the design of therapies must account for (a) the binding, catalytic, and systemic clearance properties of the therapeutic enzyme; (b) the dose and delivery regimen; (c) the biochemical and structural aspects of the thrombotic occlusion; (d) the prevailing hemodynamics and anatomical location of the thrombus; and (e) therapeutic constraints and risks of side effects. These principles also impact the design and analysis of local delivery devices.
IMMUNOLOGICAL RELATIONSHIPS OF A FILTERABLE AGENT CAUSING A LEUKEMIA IN ADULT MICE
Authors: Charlotte Friend
Journal: The Journal of Experimental Medicine (1959)

The antigenic character of a filterable agent which induces leukemia in adult mice has been investigated. Mice and rabbits injected with filtrate yielded sera which specifically neutralized infectivity of the agent. Normal sera, sera from mice with other neoplasms—including leukemias from which no causative agent has as yet been obtained,—and sera from leukemic human beings contained no such neutralizing antibody. A formalinized vaccine prepared from filtrates of leukemic spleens induced a significant degree of immunity against the agent, approximately 80 per cent of the vaccinated mice being immune on challenge with it.
The Relation of Serum Levels of Antioxidant Vitamins C and E, Retinol and Carotenoids with Pulmonary Function in the General Population
Authors: HOLGER J. SCHÜNEMANN, BRYDON J. B. GRANT, JO L. FREUDENHEIM, PAOLA MUTI, RICHARD W. BROWNE, JULIE A. DRAKE, ROBERT A. KLOCKE, MAURIZIO TREVISAN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Reduced pulmonary function is an important predictor of mortality in the general population, and antioxidant vitamins are thought to positively influence pulmonary function. Vitamin C, vitamin E, retinol, and carotenoids are powerful antioxidants but information about the joint relation of serum levels of these antioxidants to pulmonary function is limited. We analyzed the association of FEV1 and FVC with serum vitamins C and E, retinol, and carotenoids ( β -cryptoxanthin, lutein/zeaxanthin, β -carotene, and lycopene) in a cross-sectional study. The analysis was carried out in a sample of 1,616 randomly selected residents of Western New York, USA, age 35 to 79 yr and free of respiratory disease. Lung function was adjusted for height, age, sex, and race and expressed as percentage of predicted normal FEV1 (FEV1%) and FVC (FVC%). Participants in the lowest quartile of each of the serum antioxidants had consistently lower FEV1% and FVC% than those in higher quartiles. Multiple linear regression analysis revealed significant associations of vitamin C, vitamin E, β -cryptoxanthin, lutein/zeaxanthin, β -carotene, and retinol with FEV1% when these variables were investigated individually after adjustment for other covariates (smoking status, pack-years of smoking, weight, eosinophil count, and education). When all of these antioxidant vitamins were analyzed simultaneously in a multivariate regression model, the strongest association was seen with vitamin E and β -cryptoxanthin. Only retinol showed an independent effect on FEV1% after controlling for vitamin E and β -cryptoxanthin. As for FEV1%, vitamin E and β -cryptoxanthin were most strongly related to FVC% when all variables were considered in the multivariate regression model. The differences in FEV1 associated with a reduction of one standard deviation of serum vitamin E or β -cryptoxanthin were equivalent to the negative influence of approximately 1 to 2 yr of aging. Our findings support the hypothesis that antioxidant vitamins may play a role in respiratory health and that vitamin E and β -cryptoxanthin appear to be stronger correlates of lung function than other antioxidant vitamins.
mTORC1 inhibition delays growth of neurofibromatosis type 2 schwannoma
Authors: Marco Giovannini, Nicolas-Xavier Bonne, Jeremie Vitte, Fabrice Chareyre, Karo Tanaka, Rocky Adams, Laurel M. Fisher, Laurence Valeyrie-Allanore, Pierre Wolkenstein, Stephane Goutagny, Michel Kalamarides
Journal: Neuro-Oncology (2014)

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant genetic disorder, resulting in a variety of neural tumors, with bilateral vestibular schwannomas as the most frequent manifestation. Recently, merlin, the NF2 tumor suppressor, has been identified as a novel negative regulator of mammalian target of rapamycin complex 1 (mTORC1); functional loss of merlin was shown to result in elevated mTORC1 signaling in NF2-related tumors. Thus, mTORC1 pathway inhibition may be a useful targeted therapeutic approach. We studied in vitro cell models, cohorts of mice allografted with Nf2−/− Schwann cells, and a genetically modified mouse model of NF2 schwannoma in order to evaluate the efficacy of the proposed targeted therapy for NF2. We found that treatment with the mTORC1 inhibitor rapamycin reduced the severity of NF2-related Schwann cell tumorigenesis without significant toxicity. Consistent with these results, in an NF2 patient with growing vestibular schwannomas, the rapalog sirolimus induced tumor growth arrest. Taken together, these results constitute definitive evidence that justifies proceeding with clinical trials using mTORC1-targeted agents in selected patients with NF2 and in patients with NF2-related sporadic tumors.
Adherence to BSG adenoma surveillance guidelines will reduce colonoscopic workload
Authors: R C Thomas
Journal: Gut (2004)

There is an ever increasing demand for colonoscopy nationally which will increase further when colorectal cancer screening is rolled out nationally. To accommodate this, a marked improvement in the efficiency of endoscopy units is required. One simple way of reducing demand is to reduce the number of repeat procedures performed. We have found that by following the British Society of Gastroenterology (BSG) polyp follow up guidelines,1 our unit could …
Asthma medication use during pregnancy, wheeze and estimated exposure to ambient nitrogen dioxide
Authors: Janneane F. Gent, Julie M. Kezik, Melissa E. Hill, Lisa A. McKay, Theodore R. Holford, Brian P. Leaderer, Michael B. Bracken
Journal: European Respiratory Journal (2014)

Asthma affects 8–9% of pregnant women in the USA [1]. Since asthma exacerbations during pregnancy can lead to poor pulmonary function, hypoxia and other adverse health outcomes for the mother, fetus and neonate [2, 3], maintaining good control of asthma during pregnancy is recommended for the health of both mother and baby [4]. Reviews of the safety of asthma medication use during pregnancy suggest no or minimal effects on fetal growth and perinatal complications [4–6]. In spite of this, many pregnant women choose to reduce or stop their asthma medications [7]. Risk of wheeze associated with ambient NO2 exposure is higher for pregnant asthmatics who have reduced their medication <http://ow.ly/EBRFJ>
Increased Sensitivity to Corticosterone as a Possible Factor in the Development of Adrenal Regeneration Hypertension
Authors: FLOYD R. SKELTON
Journal: Circulation Research (1960)

The suggestion that the pathogenesis of adrenal-regeneration hypertension might involve sensitization to the hypertensive properties of corticosterone by the period of cortical insufficiency which follows adrenal enucleation has been investigated. Nonhypertensive doses of corticosterone were given to uninephrectomized, salt-treated and adrenalectomized rats after periods of insufficiency of variable length and to similar rats bearing regenerating adrenals, beginning such treatment at intervals after enucleation. The following conclusions have been drawn from the data obtained: (1) Adrenal cortical insufficiency for as long as 2 weeks did not sensitize to the hypertension-inducing property of corticosterone; (2) Corticosterone administration to rats bearing regenerating adrenals, beginning treatment up to 3 weeks after operation, did not enhance the development of hypertension or increase the severity of vascular lesions.
Dimensionality and explanatory power of reading models
Authors: Douglas Hanes, Gin McCollum
Journal: Behavioral and Brain Sciences (2003)

The authors' review of alternative models for reading is of great value in identifying issues and progress in the field. More emphasis should be given to distinguishing between models that offer an explanation for behavior and those that merely simulate experimental data. An analysis of a model's discrete structure can allow for comparisons of models based upon their inherent dimensionality and explanatory power.
Interleukin-1-induced alterations in glomerular proteoglycans
Authors: N Kashihara, Y Watanabe, H Makino, Y S Kanwar
Journal: Journal of the American Society of Nephrology (1992)

The effect of interleukin-1 alpha (IL-1) on the synthesis of glomerular basement membrane heparan sulfate-proteoglycan (HS-PG) was investigated. An ex vivo recirculating organ perfusion system was used. Kidneys were perfused with a medium containing (35S) sulfate and IL-1 (0.625 to 6.25 ng/mL). After radiolabeling was performed, a small cortical piece was saved for tissue autoradiography; the remaining kidney and perfusion medium were used for biochemical studies. Renal cortices were dissected out, and glomeruli were isolated; the PG were extracted and characterized. With exposure to IL-1 (5 ng/mL), an approximately twofold increase of the radioactivity in the glomerular fraction was noted. The increase was unaffected by indomethacin treatment. By Sepharose CL-6B chromatography, a single peak of radioactivity with Kav = 0.25 (macromolecular form of PG) was observed in the control group. The IL-treated group had two peaks of radioactivity with Kav = 0.25 and 0.45: the first peak contained PG, and the second peak consisted of free glycosaminoglycan (GAG) chains. Elution profiles of hydrolyzed tissue GAG chains were similar. No change in the ratio of chondroitin to heparan sulfate was observed. By DEAE-Sephacel chromatography, the glomerular PG/GAG of the IL-treated group eluted at a relatively lower salt concentration, suggesting a change in the charge density characteristics. No differences in the elution profiles of media PG/GAG were observed. (35S)methionine labeling of proteins showed no significant increase of the total radioincorporation in the IL-treated group. Immunoprecipitation studies revealed an approximately 88% increase in the de novo synthesis of PG. Tissue autoradiography revealed an approximately twofold increase of (35S) sulfate radioactivity over the glomerular mesangium, epithelium, and basement membranes. These results indicate that IL-1 enhances the synthesis of the macromolecular form of PG and the generation of free chains. Conceivably, such alterations may lead to defective macromolecular interactions among various components of the glomerular basement membrane and compromise the integrity of the ultrafiltration unit of the glomerulus.