tbuckley/cabot-search huggingface dataset:
Impaired Self-Renewal and Increased Colitis and Dysplastic Lesions in Colonic Mucosa of AKR1B8-Deficient Mice
Authors: Yi Shen, Jun Ma, Ruilan Yan, Hongyan Ling, Xiaoning Li, Wancai Yang, John Gao, Chenfei Huang, Yiwen Bu, Yu Cao, Yingchun He, Laxiang Wan, Xuyu Zu, Jianghua Liu, Mei Chris Huang, William F. Stenson, Duan-Fang Liao, Deliang Cao
Journal: Clinical Cancer Research (2014)

Ulcerative colitis and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Aldo-keto reductase 1B10 (AKR1B10) is specifically expressed in the colonic epithelium, but downregulated in colorectal cancer. This study was aimed to investigate the etiopathogenic role of AKR1B10 in ulcerative colitis and CAC.Ulcerative colitis and CAC biopsies (paraffin-embedded sections) and frozen tissues were collected to examine AKR1B10 expression. Aldo-keto reductase 1B8 (the ortholog of human AKR1B10) knockout (AKR1B8(-/-)) mice were produced to estimate its role in the susceptibility and severity of chronic colitis and associated dysplastic lesions, induced by dextran sulfate sodium (DSS) at a low dose (2%). Genome-wide exome sequencing was used to profile DNA damage in DSS-induced colitis and tumors.AKR1B10 expression was markedly diminished in over 90% of ulcerative colitis and CAC tissues. AKR1B8 deficiency led to reduced lipid synthesis from butyrate and diminished proliferation of colonic epithelial cells. The DSS-treated AKR1B8(-/-) mice demonstrated impaired injury repair of colonic epithelium and more severe bleeding, inflammation, and ulceration. These AKR1B8(-/-) mice had more severe oxidative stress and DNA damage, and dysplasias were more frequent and at a higher grade in the AKR1B8(-/-) mice than in wild-type mice. Palpable masses were seen in the AKR1B8(-/-) mice only, not in wild-type.AKR1B8 is a critical protein in the proliferation and injury repair of the colonic epithelium and in the pathogenesis of ulcerative colitis and CAC, being a new etiopathogenic factor of these diseases.
THE TREATMENT OF CHRONIC MALARIA
Authors: T. S. Dixson
Journal: BMJ (1923)

BImTsI I 30, 1 I K Z ~~~~~~~~~~~~~M D I C A L JOUBEA& OS slow and relapses are apt to occur if the lids are separated too soon.Ultimate transparency of the Cornea depends largely on complete protection of the delicate corneal sur- face and freedom from infection.Median tarsorrhaphy lightly closes the eye as in sleep, compellinig it to "hibernate" until its reflex protective mechanism is restored.
Economic consequences of overweight and obesity in infertility: a framework for evaluating the costs and outcomes of fertility care
Authors: A.M.H. Koning, W.K.H. Kuchenbecker, H. Groen, A. Hoek, J.A. Land, K.S. Khan, B.W.J. Mol
Journal: Human Reproduction Update (2010)

Overweight and obesity are an epidemic in Western society, and have a strong impact on fertility. We studied the consequences of overweight and obesity with respect to fecundity, costs of fertility treatment and pregnancy outcome in subfertile women. We searched the literature for systematic reviews and large studies reporting on the effect of weight on both fecundity and pregnancy outcome in subfertile women. We collected data on costs of treatment with ovulation induction, intrauterine insemination and in vitro fertilization, as well as costs of pregnancy complications. We calculated, for ovulatory and anovulatory women separately, the number of expected pregnancies, complications and costs in a hypothetical cohort of 1000 normal weight, overweight and obese women each. In our hypothetical cohort of 1000 women, compared with women with normal weight, live birth was decreased by 14 and 15% (from 806 live births to 692 and 687 live births) in overweight and obese anovulatory women, respectively, for ovulatory women it was decreased by 22 and 24% (from 698 live births to 546 and 531 live births), respectively. These outcomes were associated with an increase in the number of complications and associated costs leading to cost per live birth in anovulatory overweight and obese women were 54 and 100% higher than their normal weight counterparts, for ovulatory women they were 44 and 70% higher, respectively. Overweight and obese subfertile women have a reduced probability of successful fertility treatment and their pregnancies are associated with more complications and higher costs.
Brain tumor tandem targeting using a combination of monoclonal antibodies attached to biopoly(β-l-malic acid)
Authors: Manabu Fujita, Bong-Seop Lee, Natalya M. Khazenzon, Manuel L. Penichet, Kolja A. Wawrowsky, Rameshwar Patil, Hui Ding, Eggehard Holler, Keith L. Black, Julia Y. Ljubimova
Journal: Journal of Controlled Release (2007)
β-Catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts
Authors: L Masuelli
Journal: Cardiovascular Research (2003)

Objective: To evaluate whether cardiomyocyte membrane structure and cell/extracellular matrix adhesion alterations perturb the cadherin/catenin complex in the hypertrophic cardiomyopathy (HCM). Methods: Hypertrophic cardiomyopathic hamster (UM-X7.1 strain) and human hearts were studied by light and electron microscopy, Northern and Western blot analyses and immunohistochemistry. Results: Intercalated disks are disorganized in both hamster and human cardiomyopathic hearts; β-catenin is increased and accumulated in intercalated disks depriving cardiomyocyte nuclei of fundamental signals. The accumulation of β-catenin is post-translationally regulated by an increased Wnt expression, a simultaneous decrease in glycogen synthase kinase 3β (GSK3β) expression and a different expression pattern of adenomatous polyposis coli (APC) isoforms. Conclusion: The reorganization of cell/cell adhesion in cardiomyopathic hearts is mainly contributed by the cadherin/catenin system, which is differently regulated to sustain cell structural rather than signalling needs causing considerable consequences in the determination of cardiomyocyte phenotype and clinical outcome. The accumulation of β-catenin in intercalated disks could concur to increase myocardial wall stiffness and left ventricular end-diastolic pressure (LVEDP) in hypertrophic cardiomyopathic hamster and human hearts.
Absolute and Attributable Risks of Atrial Fibrillation in Relation to Optimal and Borderline Risk Factors
Authors: Rachel R. Huxley, Faye L. Lopez, Aaron R. Folsom, Sunil K. Agarwal, Laura R. Loehr, Elsayed Z. Soliman, Rich Maclehose, Suma Konety, Alvaro Alonso
Journal: Circulation (2011)

Atrial fibrillation (AF) is an important risk factor for stroke and overall mortality, but information about the preventable burden of AF is lacking. The aim of this study was to determine what proportion of the burden of AF in blacks and whites could theoretically be avoided by the maintenance of an optimal risk profile.This study included 14 598 middle-aged Atherosclerosis Risk in Communities (ARIC) Study cohort members. Previously established AF risk factors, namely high blood pressure, elevated body mass index, diabetes mellitus, cigarette smoking, and prior cardiac disease, were categorized into optimal, borderline, and elevated levels. On the basis of their risk factor levels, individuals were classified into 1 of these 3 groups. The population-attributable fraction of AF resulting from having a nonoptimal risk profile was estimated separately for black and white men and women. During a mean follow-up of 17.1 years, 1520 cases of incident AF were identified. The age-adjusted incidence rates were highest in white men and lowest in black women (7.45 and 3.67 per 1000 person-years, respectively). The overall prevalence of an optimal risk profile was 5.4% but varied according to race and gender: 10% in white women versus 1.6% in black men. Overall, 56.5% of AF cases could be explained by having ≥ 1 borderline or elevated risk factors, of which elevated blood pressure was the most important contributor.As with other forms of cardiovascular disease, more than half of the AF burden is potentially avoidable through the optimization of cardiovascular risk factors levels.
Molecular Pathways: ROS1 Fusion Proteins in Cancer
Authors: Kurtis D. Davies, Robert C. Doebele
Journal: Clinical Cancer Research (2013)

Genetic alterations that lead to constitutive activation of kinases are frequently observed in cancer. In many cases, the growth and survival of tumor cells rely upon an activated kinase such that inhibition of its activity is an effective anticancer therapy. ROS1 is a receptor tyrosine kinase that has recently been shown to undergo genetic rearrangements in a variety of human cancers, including glioblastoma, non-small cell lung cancer (NSCLC), cholangiocarcinoma, ovarian cancer, gastric adenocarcinoma, colorectal cancer, inflammatory myofibroblastic tumor, angiosarcoma, and epithelioid hemangioendothelioma. These rearrangements create fusion proteins in which the kinase domain of ROS1 becomes constitutively active and drives cellular proliferation. Targeting ROS1 fusion proteins with the small-molecule inhibitor crizotinib is showing promise as an effective therapy in patients with NSCLC whose tumors are positive for these genetic abnormalities. This review discusses the recent preclinical and clinical findings on ROS1 gene fusions in cancer.
Over-representation of construction-related occupations in male patients with systemic sclerosis
Authors: V Smith, M Vanthuyne, B Vander Cruyssen, J Van Praet, F Vermeiren, H Smets, F Houssiau, F De Keyser
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Aims:</h3> Based on preliminary observations, we tested the hypothesis that construction-related occupations are associated with systemic sclerosis (SSc). <h3>Methods:</h3> The professional occupation of 91 patients with SSc (71 females and 20 males) was recorded. Categorisation into construction-related and other professions was performed. A double definition was used for construction-related occupations. The first (limited) definition was based upon categories of the Belgian National Institute of Statistics (NIS) occupational list. The following occupations were considered construction-related: electricians, joiners, masons and tilers, plumbers and pipefitters. The use of this list also allows us to compare the distribution of professions in these patients with that in the general population. As the NIS occupational list is limitative and leaves out some "real-life" construction-related occupations, a second and broader interpretation was given to the concept of construction-related occupations. <h3>Results:</h3> The prevalence of construction-related professions in males with SSc, according to the limited definition, was 10-fold higher than in the general working population (50% vs 5%; p&lt;0.001). Interestingly, most of the patients with construction-related occupations were electricians. In the broader interpretation, 75% of the men with SSc fell into the category of construction-related occupations. <h3>Conclusions:</h3> The data show an association between SSc and professional occupation.
Fibrinogen and fibronectin binding cooperate for valve infection and invasion in <i>Staphylococcus aureus</i> experimental endocarditis
Authors: Yok-Ai Que, Jacques-Antoine Haefliger, Lionel Piroth, Patrice François, Eleonora Widmer, José M. Entenza, Bhanu Sinha, Mathias Herrmann, Patrick Francioli, Pierre Vaudaux, Philippe Moreillon
Journal: The Journal of Experimental Medicine (2005)

The expression of Staphylococcus aureus adhesins in Lactococcus lactis identified clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) as critical for valve colonization in rats with experimental endocarditis. This study further analyzed their role in disease evolution. Infected animals were followed for 3 d. ClfA-positive lactococci successfully colonized damaged valves, but were spontaneously eradicated over 48 h. In contrast, FnBPA-positive lactococci progressively increased bacterial titers in vegetations and spleens. At imaging, ClfA-positive lactococci were restricted to the vegetations, whereas FnBPA-positive lactococci also invaded the adjacent endothelium. This reflected the capacity of FnBPA to trigger cell internalization in vitro. Because FnBPA carries both fibrinogen- and fibronectin-binding domains, we tested the role of these functionalities by deleting the fibrinogen-binding domain of FnBPA and supplementing it with the fibrinogen-binding domain of ClfA in cis or in trans. Deletion of the fibrinogen-binding domain of FnBPA did not alter fibronectin binding and cell internalization in vitro. However, it totally abrogated valve infectivity in vivo. This ability was restored in cis by inserting the fibrinogen-binding domain of ClfA into truncated FnBPA, and in trans by coexpressing full-length ClfA and truncated FnBPA on two separate plasmids. Thus, fibrinogen and fibronectin binding could cooperate for S. aureus valve colonization and endothelial invasion in vivo.
Endogenous pyrogen production by Hodgkin's disease and human histiocytic lymphoma cell lines in vitro.
Authors: P Bodel, P Ralph, K Wenc, J C Long
Journal: Journal of Clinical Investigation (1980)

Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous pyrogen from the two cell lines was similar and closely resembled that produced by normal human monocytes in antigenic properties as well as heat and pronase sensitivity. The Hodgkin's disease and histiocytic lymphoma cell lines do not require specific stimulation for the production of endogenous pyrogen suggesting that the mechanism of pyrogen release by neoplastic macrophage-related cells differs from that of normal phagocytic cells. The tumor-associated fever in some patients with malignant lymphoma may be caused by a release of endogenous pyrogen by proliferating neoplastic cells.
Social versus reproductive success: The central theoretical problem of human sociobiology
Authors: Daniel R. Vining
Journal: Behavioral and Brain Sciences (1986)

Abstract The fundamental postulate of sociobiology is that individuals exploit favorable environments to increase their genetic representation in the next generation. The data on fertility differentials among contemporary humans are not cotvietent with this postulate. Given the importance of Homo sapiens as an animal species in the natural world today, these data constitute particularly challenging and interesting problem for both human sociobiology and sociobiology as a whole. The first part of this paper reviews the evidence showing an inverse relationship between reproductive fitness and “endowment” (i.e. wealth, success, and measured aptitudes) in contemporary, urbanized societies. It is shown that a positive relationship is observed only for those cohorts who bore their children during a unique period of rising fertility, 1935–1960, and that these cohorts are most often cited by sociobiologists as supporting the central postulate of sociobiology. Cohorts preceding and following these show the characteristic inverse relationship between endowment and fertility. The second section reviews the existing so-ciobiological models of this inverse relationship, namely, those of Barkow, Burley, and Irons, as well as more informal responses among sociobiologists to the persistent violation of sociobiology's central postulate, such as those of Alexander and Dawkins. The third section asks whether the goals of sociobiology, given the violation of its fundamental postulate by contemporary human societies, might not be better thought of as applied rather than descriptive, with respect to these societies. A proper answer to this question begins with the measurement of the pace and direction of natural selection within modern human populations, as compared to other sources of change. The vast preponderance of the shifts in human trait distributions, including the IQ distribution, appears to be due to environmental rather than genetic change. However, there remains the question of just how elastic these distributions are in the absence of reinforcing genetic change.
Pulmonary Function in Adults with Intracardiac Septal Defect
Authors: C. R. WOOLF
Journal: Circulation (1963)

Pulmonary function has been assessed in 45 patients with atrial or ventricular septal defect. Moderate and severe dyspnea occurred almost exclusively in patients with high pulmonary artery pressure irrespective of whether this was due to high pulmonary blood flow or high pulmonary vascular resistance. Evidence is presented suggesting that this raised pulmonary artery pressure causes lung damage shown by a low compliance and high nonelastic resistance. These findings suggest an abnormal alveolar-capillary membrane and an abnormality of ventilation-perfusion relationships, which in turn cause a relatively low pulmonary diffusing capacity requiring excessive hyperventilation on exercise to maintain oxygen requriments. In patients with moderate or severe dyspnea, the abnormally high minute volume of ventilation during mild exertion is associated with a high work of breathing, the dual abnormality separating them from patients with only slight dyspnea on exertion.
Serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease
Authors: Min-Sun Kwak, Donghee Kim, Goh Eun Chung, Seung Joo Kang, Min Jung Park, Yoon Jun Kim, Jung-Hwan Yoon, Hyo-Suk Lee
Journal: Clinical and Molecular Hepatology (2012)

See the commentary-article "Elevated serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease" on page 357.
Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma
Authors: O. Bailon, K. Chouahnia, A. Augier, T. Bouillet, S. Billot, I. Coman, R. Ursu, C. Belin, L. Zelek, G. Des Guetz, C. Levy, A. F. Carpentier, J.-F. Morere
Journal: Neuro-Oncology (2012)

Approximately 10% of patients with non-small cell lung cancer (NSCLC) have brain metastases at the time of diagnosis. When surgical resection is not possible, whole brain radiotherapy is the standard of care, with a cerebral response rate of approximately 30%. We report our experience with an upfront association of carboplatin and pemetrexed (areas under the curve, 5 and 500 mg/m2, respectively), every 3 weeks, in 30 patients presenting with newly diagnosed brain metastases and NSCLC. Cerebral MRIs were performed every 6–9 weeks. The radiologic response rates were assessed according to Response Evaluation Criteria in Solid Tumors. Overall survival was also determined. Twenty-six patients were evaluable for response, and the objective cerebral response rate (complete and partial response) in the intent-to-treat population was 40% (12 of 30 patients). Event-free survival was 31 weeks, and median overall survival was 39 weeks. The upfront association of carboplatin plus pemetrexed allows simultaneous treatment of cerebral and systemic disease in patients with NSCLC with newly diagnosed brain metastases and appears to be particularly interesting in terms of radiologic response and overall survival. Further clinical studies are warranted.
CD4+ T-Cell Help in the Tumor Milieu Is Required for Recruitment and Cytolytic Function of CD8+ T Lymphocytes
Authors: Rinke Bos, Linda A. Sherman
Journal: Cancer Research (2010)

CD4 help for CD8(+) T lymphocytes prevents tolerance and promotes the survival of effector and memory CD8(+) T cells. Here, we describe additional helper functions that require CD4(+) T cells within the tumor environment. CD8(+) T-cell recruitment, proliferation, and effector function within the tumor were greatly enhanced by tumor-specific CD4(+) T cells. Recruitment of CD8(+) T cells was accelerated by IFN-γ-dependent production of chemokines. Production of interleukin-2 by tumor resident CD4(+) T cells enhanced CD8(+) T-cell proliferation and upregulated expression of granzyme B. These results highlight a novel role for tumor-specific CD4(+) T cells in promoting CD8(+) T-cell recruitment and cytolytic function, two previously unappreciated aspects of tumor-specific CD4 help.
Airway Hyperresponsiveness in Elite Athletes
Authors: JEAN-BRUNO LANGDEAU, HÉLÈNE TURCOTTE, DENNIS M. BOWIE, JEAN JOBIN, PIERRE DESGAGNÉ, LOUIS-PHILIPPE BOULET
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

It has been suggested that high-level training could contribute to the development of airway hyperresponsiveness (AHR), but the comparative effects of different sports on airway function remains to be determined. We evaluated 150 nonsmoking volunteers 18 to 55 yr of age; 100 athletes divided into four subgroups of 25 subjects each according to the predominant estimated hydrocaloric characteristic of ambient air inhaled during training: dry air (DA), cold air (CA), humid air (HA) and a mixture of dry and humid air (MA), and 50 sedentary subjects. Each subject had a respiratory questionnaire, a methacholine challenge, allergy skin-prick tests, and heart rate variability recording for evaluation of parasympathetic tone. The athletes had a 49% prevalence of AHR (PC20 < 16 mg/ml), with a mean PC20 of 16.9 mg/ml, compared with 28% (PC20: 35.4) in sedentary subjects (p = 0.009). The prevalence (%) of AHR and mean PC20 (mg/ml) varied as followed in the four subgroups of athletes: DA: 32% and 30.9; CA: 52% and 15.8; HA: 76% and 7.3; and MA: 32% and 21.5 (p = 0.002). The estimated parasympathetic tone was higher in athletes (p < 0.001), but this parameter showed only a weak correlation with PC20 (r = − 0.17, p = 0.04). This study has shown a significantly higher prevalence of AHR in athletes than in the control group because of the higher prevalence in the CA and HA groups. Parasympathetic activity may act as modulator of airway responsiveness, but the increased prevalence of AHR in our athlete population may be related to the type and possibly the content of inhaled air during training.