tbuckley/cabot-search huggingface dataset:
Clinical Aspects of Sucrose and Fructose Metabolism
Authors: John P Bantle
Journal: Diabetes Care (1989)

The per capita consumption of sugars in the United States accounts for approximately 21% of total calorie intake. Most Americans eat and enjoy sugar-containing foods every day, but the use of sugars in the diabetic diet has traditionally been proscribed for fear of aggravating hyperglycemia. However, short-term and most longer-term studies demonstrate that dietary sucrose does not cause a greater postprandial rise in plasma glucose than isocaloric amounts of other common carbohydrates. The available evidence suggests that sucrose has a glycemic effect similar to that of bread, potatoes, and rice. Dietary fructose, in contrast, may produce a lesser postprandial rise in plasma glucose than other common carbohydrates. There is considerable controversy about the effects of dietary sucrose and fructose on serum lipids, and their effects on other metabolic events, such as the nonenzymatic glycosylation of proteins, are uncertain. Nevertheless, it is reasonable to allow diabetic patients to consume sugar-containing foods as long as they do so in a controlled fashion.
Phase II study of paclitaxel in patients with relapsed or cisplatin-refractory testicular cancer
Authors: C. Bokemeyer, J. Beyer, B. Metzner, U. Rüther, A. Harstrick, L. Weißbach, U. Köhrmann, W. Verbeek, H.-J. Schmoll
Journal: Annals of Oncology (1996)
Evaluation of Stepped Care for Chronic Pain (ESCAPE) in Veterans of the Iraq and Afghanistan Conflicts
Authors: Matthew J. Bair, Dennis Ang, Jingwei Wu, Samantha D. Outcalt, Christy Sargent, Carol Kempf, Amanda Froman, Arlene A. Schmid, Teresa M. Damush, Zhangsheng Yu, Louanne W. Davis, Kurt Kroenke
Journal: JAMA Internal Medicine (2015)

Despite the prevalence and the functional, psychological, and economic impact of chronic pain, few intervention studies of treatment of chronic pain in veterans have been performed.To determine whether a stepped-care intervention is more effective than usual care, as hypothesized, in reducing pain-related disability, pain interference, and pain severity.We performed a randomized clinical trial comparing stepped care with usual care for chronic pain. We enrolled 241 veterans from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn with chronic (>3 months) and disabling (Roland Morris Disability Scale score, ≥7) musculoskeletal pain of the cervical or lumbar spine or extremities (shoulders, knees, and hips) in the Evaluation of Stepped Care for Chronic Pain (ESCAPE) trial from December 20, 2007, through June 30, 2011. The 9-month follow-up was completed by April 2012. Patients received treatment at a postdeployment clinic and 5 general medicine clinics at a Veterans Affairs medical center.Step 1 included 12 weeks of analgesic treatment and optimization according to an algorithm coupled with pain self-management strategies; step 2, 12 weeks of cognitive behavioral therapy. All intervention aspects were delivered by nurse care managers.Pain-related disability (Roland Morris Disability Scale), pain interference (Brief Pain Inventory), and pain severity (Graded Chronic Pain Scale).The primary analysis included 121 patients receiving the stepped-care intervention and 120 patients receiving usual care. At 9 months, the mean decrease from baseline in the Roland Morris Disability Scale score was 1.7 (95% CI, -2.6 to -0.9) points in the usual care group and 3.7 (95% CI, -4.5 to -2.8) points in the intervention group (between-group difference, -1.9 [95% CI, -3.2 to -0.7] points; P=.002). The mean decrease from baseline in the Pain Interference subscale score of the Brief Pain Inventory was 0.9 points in the usual care group and 1.7 points in the intervention group (between-group difference, -0.8 [95% CI, -1.3 to -0.3] points; P=.003). The Graded Chronic Pain Scale severity score was reduced by 4.5 points in the usual care group and 11.1 points in the intervention group (between-group difference, -6.6 [95% CI, -10.5 to -2.7] points; P=.001).A stepped-care intervention that combined analgesics, self-management strategies, and brief cognitive behavioral therapy resulted in statistically significant reductions in pain-related disability, pain interference, and pain severity in veterans with chronic musculoskeletal pain.clinicaltrials.gov Identifier: NCT00386243.
Nuclear Alternate Estrogen Receptor GPR30 Mediates 17β-Estradiol–Induced Gene Expression and Migration in Breast Cancer–Associated Fibroblasts
Authors: Antonio Madeo, Marcello Maggiolini
Journal: Cancer Research (2010)

Fibroblasts are the principal cellular component of connective tissue and are associated with cancer cells at all stages of tumor progression. Structural and functional contributions of fibroblasts to the growth, survival, and invasive capacity of cancer cells are beginning to emerge. In breast carcinoma, approximately 80% of stromal fibroblasts termed cancer-associated fibroblasts (CAF) are thought to manifest an activated phenotype that promotes cancer cell proliferation tumor growth at metastatic sites similar to the primary tumor. In this report, we show that CAFs respond to physiologic concentrations of 17beta-estradiol (E2) by rapidly inducing extracellular signal-regulated kinase phosphorylation and immediate early gene expression, including c-fos and connective tissue growth factor, and cyclin D1. Notably, the E2 response is mediated by the alternate estrogen receptor GPR30, which interfaces with the epidermal growth factor receptor (EGFR) signaling pathway. In particular, E2 stimulates a physical interaction between GPR30 and phosphorylated EGFR, recruiting them to the cyclin D1 gene promoter. Nuclear localization induced by E2 was confirmed by cellular immunofluorescence methods. GPR30 was required for CAF proliferation and migration induced by E2. Our results provide important new mechanistic insights into how CAFs are stimulated by estrogen through a GPR30-mediated nuclear signaling pathway. More generally, they define estrogenic GPR30 signaling as a functionally important component of the tumor microenvironment.
Arthritis and endogenous glucocorticoids: the emerging role of the 11 -HSD enzymes
Authors: F. Buttgereit, H. Zhou, M. J Seibel
Journal: Annals of the Rheumatic Diseases (2007)

It is somewhat in contrast to the great importance of synthetic glucocorticoids in the systemic and intra-articular treatment of rheumatoid arthritis (RA) and other inflammatory rheumatic diseases1–3 that we do not know whether endogenous glucocorticoid action contributes to the susceptibility and/or severity of RA. In this issue of the journal, Hardy and colleagues describe an interesting study into the local and systemic metabolism of endogenous glucocorticoids in inflammatory arthritis ( see page 1204 ).4 Their findings demonstrate the existence of substantial glucocorticoid metabolism in the joint. Thus, the synovial tissue is reported to predominantly activate glucocorticoids through the action of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In patients with RA, the activity of this enzyme was found to correlate positively with donor erythrocyte sedimentation rate (ESR). Interestingly, 11β-HSD1 expression was primarily seen in fibroblasts. However, synovial tissue seems also able to convert active cortisol back to inactive cortisone. This pathway is driven by synovial macrophages expressing a glucocorticoid-inactivating enzyme, 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). In order to better understand these findings, we should first like to give a short overview of how endogenous glucocorticoids are regulated and metabolised on a cellular level, and the roles of 11β-HSD enzymes in the latter process.

Endogenous glucocorticoids are regulated via the hypothalamic–pituitary–adrenal axis and control electrolyte and fluid homoeostasis, fuel metabolism and immune and stress responses.5–10 Cortisol acts primarily through activation of the cognate intracellular glucocorticoid receptor at the target tissues. However, cytokines, growth factors and specific enzymes modulate this control at a local level.11 12

For a long time, it was thought that glucocorticoid actions …
Acinar redistribution and heterogeneity in transport of the organic cation rhodamine B in rat liver
Authors: Ineke Braakman, Geny Martha Maria Groothuis, Dirk Klaas Fokke Meijer
Journal: Hepatology (1987)

We studied a possible acinar heterogeneity in the transport of organic cations, using rhodamine B as model compound. Employing perfusions of isolated rat livers in the ante- and retrograde mode and quantitative fluorescence microscopy, Zones 1 and 3 were shown to be equally efficient in taking up rhodamine B. Ten minutes after injection in an antegrade perfusion, 95% of the dose was localized in the portal half of the acinus. Fifty minutes later, however, the amount of rhodamine B in Zone 1 had been reduced to 23%; 30 and 31% were in Zones 2 and 3, respectively, and the medium concentration was doubled. Thus, unchanged rhodamine B appeared to be transported downstream within the liver, either via the medium or directly from cell to cell, finally resulting in a relatively higher rhodamine B concentration in Zone 3. To obtain additional data, we designed a perfusion setup in which the zones could be studied separately. In both zones, the amount excreted into the medium was about 30 times the amount excreted into bile. Intracellular sequestration of rhodamine B and the rate constant for sinusoidal secretion were higher in Zone 3, while the sinusoidal uptake rates were equal; biliary excretion was higher in Zone 1. Acinar distribution changed with time because rhodamine B, primarily accumulated in Zone 1, was secreted into the sinusoids and taken up again by downstream cells. The finally higher rhodamine B concentration in Zone 3 was caused by a zonal heterogeneity in intracellular sequestration and sinusoidal secretion of rhodamine B.
Syphilitic Gummatous Tumour of the Brain: With Remarks
Authors: S. M. Bradley
Journal: BMJ (1873)

abundantly deposited in the surrounding skin, so that, in fact, the margin was better defined than heretofore.The whole on each side was set in a dark brown framework.About this time, a single small patch of similar erythema was developed on the forehead towards the roots of the hair; and I had an opportunity of remarking that where it encroached on the scalp, the hair was shed precisely as in alopecia.The case seems to come under the head of morphcea or vitiligo, and to stand in correspondence with the foregoing cases.They all seem re- motely allied to that degeneration and decay which is evident in the vitiligo and loss of hair observed in drop evil and elephantiasis.
Autonomic control of cardiovascular performance and whole body O2 delivery and utilization in swine during treadmill exercise
Authors: R Stubenitsky
Journal: Cardiovascular Research (1998)

Objective: The present study determined the role of the autonomic nervous system (ANS) in the regulation of systemic and pulmonary circulation and of O2 delivery and utilization in swine at rest and during graded treadmill exercise. Methods: Instrumented swine (n=12) were subjected to treadmill exercise (1–5 km/h) under control conditions and in the presence of single and combined β-adrenergic, α-adrenergic and muscarinic (M) receptor blockade. Results: Exercise produced a four-fold increase in body O2 consumption, due to a doubling of both cardiac output and the arterio–mixed-venous O2 content difference. The latter resulted from an increase in O2 extraction, from 45±1% at rest to 74±1% at 5 km/h, as the O2 carrying capacity [haemoglobin concentration (Hb)] increased by only ∼10%. The increase in cardiac output resulted from a doubling of the heart rate and a small (<10%) increase in stroke volume. The mean aortic pressure (MAP) was unchanged, implying a 50% decrease in systemic vascular resistance (P≤0.05). In contrast, exercise had no significant effect on pulmonary vascular resistance. The sympathetic division of the ANS-controlled O2 delivery via β-adrenoceptors (heart rate and contractility) and Hb concentration via α-adrenoceptor-mediated splenic contraction. In addition, the sympathetic division modulated systemic vascular tone via α- and β-adrenoceptors, but also exerted a vasodilator influence on the pulmonary circulation via β-adrenoceptors. The parasympathetic division controlled O2 delivery in part directly (heart rate) and in part indirectly via inhibition of β-adrenoceptor activity (heart rate and contractility), even during heavy exercise. In addition, the parasympathetic division exerted a direct vasodilator influence on the pulmonary, but not on the systemic, circulation. Conclusions: Thus, in swine, in a manner similar to that in humans, both the sympathetic and parasympathetic division of the ANS contribute to cardiovascular homeostasis during exercise up to levels of high intensity.
Rhythmic Control of the ARF-MDM2 Pathway by ATF4 Underlies Circadian Accumulation of p53 in Malignant Cells
Authors: Michiko Horiguchi, Satoru Koyanagi, Ahmed M. Hamdan, Keisuke Kakimoto, Naoya Matsunaga, Chikamasa Yamashita, Shigehiro Ohdo
Journal: Cancer Research (2013)

The sensitivity of cancer cells to chemotherapeutic agents varies according to circadian time. Most chemotherapeutic agents ultimately cause cell death through cell-intrinsic pathways as an indirect consequence of DNA damage. The p53 tumor suppressor gene (TRP53) configures the cell deaths induced by chemotherapeutic agents. In this study, we show that the transcription factor ATF4, a component of the mammalian circadian clock, functions in circadian accumulation of p53 protein in tumor cells. In murine fibroblast tumor cells, ATF4 induced the circadian expression of p19ARF (Cdkn2a). Oscillation of p19ARF interacted in a time-dependent manner with MDM2, a specific ubiquitin ligase of p53, resulting in a rhythmic prevention of its degradation by MDM2. Consequently, the half-life of p53 protein varied in a circadian time-dependent manner without variation in mRNA levels. The p53 protein accumulated during those times when the p19ARF-MDM2 interaction was facilitated. Notably, the ability of the p53 degradation inhibitor nutlin-3 to kill murine fibroblast tumor cells was enhanced when the drug was administered at those times of day during which p53 had accumulated. Taken together, these results suggested that ATF4-mediated regulation of the p19ARF-MDM2 pathway underlies the circadian accumulation of p53 protein in malignant cells. Furthermore, they suggest an explanation for how the sensitivity of cancer cells to chemotherapeutic agents is enhanced at those times of day when p53 protein has accumulated, as a result of circadian processes controlled by ATF4.
Multiple biological activities of human recombinant interleukin 1.
Authors: C A Dinarello, J G Cannon, J W Mier, H A Bernheim, G LoPreste, D L Lynn, R N Love, A C Webb, P E Auron, R C Reuben
Journal: Journal of Clinical Investigation (1986)

Complementary DNA coding for human monocyte interleukin 1 (IL-1), pI 7 form, was expressed in Escherichia coli. During purification, IL-1 activity on murine T cells was associated with the recombinant protein. Homogeneous human recombinant IL-1 (hrIL-1) was tested in several assays to demonstrate the immunological and inflammatory properties attributed to this molecule. hrIL-1 induced proliferative responses in a cloned murine T cell in the presence of suboptimal concentrations of mitogen, whereas no effect was observed with hrIL-1 alone. At concentrations of 0.05 ng/ml, hrIL-1 doubled the response to mitogen (5 X 10(6) half maximal units/mg). Human peripheral blood T cells depleted of adherent cells underwent a blastogenic response and released interleukin 2 in the presence of hrIL-1 and mitogen. hrIL-1 was a potent inflammatory agent by its ability to induce human dermal fibroblast prostaglandin E2 production in vitro and to produce monophasic (endogenous pyrogen) fever when injected into rabbits or endotoxin-resistant mice. These studies establish that the dominant pI 7 form of recombinant human IL-1 possesses immunological and inflammatory properties and acts on the central nervous system to produce fever.
Expression of Neuroendocrine Markers in Undifferentiated Carcinomas of the Gastrointestinal Tract
Authors: Patricia Grabowski, Hans Scherübl
Journal: Journal of Clinical Oncology (2005)

of the Journal of Clinical Oncology, Brenner et al 1 have provided an excellent review on small-cell undifferentiated carcinomas of the gastrointestinal tract.However, we want to point out that immunohistochemical staining for neuroendocrine markers is often positive in undifferentiated gastrointestinal cancers.In a recent series of 20 undifferentiated colorectal cancers, representing 0.8% of 2,530 colorectal cancers treated at a single institution, nine (45%) of the 20 undifferentiated cancers were found to express neuroendocrine markers. 2 Interestingly, neuroendocrine marker-positive undifferentiated cancers differed from neuroendocrine marker-negative undifferentiated cancers in the expression of epidermal growth factor receptor (EGFR).Although none of the nine neuroendocrine marker-positive cancers stained positive for EGFR expression, the 11 neuroendocrine marker-negative cancers expressed EGFR immunohistochemically (see Fig 1).Moreover, neuroendocrine differentiation was of prognostic relevance.Neuroendocrine marker-negative undifferentiated colorectal cancers were diagnosed at an earlier stage and had a more favorable overall survival than neuroendocrine marker-positive undifferentiated colorectal carcinomas (45% v 11% survivors after 2 years; P Ͻ .001).The latter manifested at an earlier age (51.9 years v 63.6 years), a finding that may well reflect their aggressive tumor biology.Noteworthy is the fact that partial neuroendocrine differentiation also predicts a less favorable clinical course in Dukes' C colorectal adenocarcinoma. 3ndifferentiated neuroendocrine carcinomas are not thought to derive from benign orthotopic neuroendocrine epithelial cells 4 ; instead, the most favored concept currently is that they are of stem cell origin.This means that a single epithelial cell, even if malignant, can give rise to all cell types seen in the colorectal epithelium. 5This concept also explains the occurrence of bi-or multiphenotypic tumors.In line with this notion, Vortmeyer et al 6 observed identical genetic alterations in synchronous poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas.We suggest that the expression of neuroendocrine markers should be evaluated in undifferentiated carcinomas of the gastrointestinal tract, because neuroendocrine differentiation is of prognostic value and will probably have therapeutic implications in the near future.
Experts disagree on whether cost of publishing research will fall, as open access grows, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2013)

Experts in research and publishing disagree over whether the cost of getting research published is likely to drop as the United Kingdom moves to an open access system for published studies.

MPs on the parliamentary business, innovation, and skills committee quizzed witnesses on 16 April as part of their inquiry into the government’s open access policy.

The government has accepted the recommendations of the Finch group report Accessibility, Sustainability, Excellence: How to Expand Access to Research Publications , published in June last year, for a system of publishing research in open access or hybrid journals, funded by article processing charges (APCs).1 2

The group and the government’s preference is for a “gold” model of open access, in which …
Do not-for-profit nursing homes provide better quality?
Authors: R T. Konetzka
Journal: BMJ (2009)

<h3>Introduction</h3> Intimate partner violence detrimentally affects the social and emotional well-being of children and mothers. These two populations are impacted both individually and within the context of their relationship with one another. Child mental health, maternal mental health and the mother–child relationship may be impaired as a consequence. Early intervention to prevent or arrest impaired mother–child attachment and child development is needed. Dyadic or relational mental health interventions that include mothers with their children, such as child–parent psychotherapy, are effective in improving the mental health of both children and mothers and also strengthening their relationship. While child–parent psychotherapy has been trialled overseas in several populations, Australian research on relational interventions for children and women recovering from violence is limited. This study aims to assess the acceptability and feasibility of implementing child–parent psychotherapy in Australian families. <h3>Methods and analysis</h3> Using a mixed methods, prepost design this feasibility study will examine the acceptability of the intervention to women with preschool aged children (3–5 years, n=15 dyads) and providers, and identify process issues including recruitment, retention and barriers to implementation and sustainability. In addition, intervention efficacy will be assessed using maternal and child health outcomes and functioning, and mother–child attachment measures. Young children’s mental health needs are underserviced in Australia. More research is needed to fully understand parenting in the context of intimate partner violence and what works to help women and children recover. If the intervention is found to be feasible, findings will inform future trials and expansion of child–parent psychotherapy in Australia. <h3>Ethics and dissemination</h3> Ethics approval obtained from clinical sites and the La Trobe University Human Research Ethics Committee (ID: HEC17-108). Results will be disseminated through conference proceedings and academic publications.
Construction of Soluble Mamu-B*1703, a Class I Major Histocompatibility Complex of Chinese Rhesus Macaques, Monomer and Tetramer Loaded with a Simian Immunodeficiency Virus Peptide
Authors: Dongyun Ouyang, Xiaoying Wang, Xianhui He, Lihui Xu, Huanjing Shi, Qi Gao, He Guo
Journal: Cellular and Molecular Immunology (2009)
C5b-9 dimer: isolation from complement lysed cells and ultrastructural identification with complement-dependent membrane lesions.
Authors: G Biesecker, E R Podack, C A Halverson, H J Müller-Eberhard
Journal: The Journal of Experimental Medicine (1979)

The membrane attack complex (MAC) of complement was extracted from the membranes of cells lysed by human complement and its properties were compared with those of the fluid phase complex SC5b-9. Upon sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunochemical analysis, the two isolated complexes had identical subunit compositions, except that the MAC lacked the S-protein. The sedimentation coefficient and molecular weight of the extracted and isolated MAC were, respectively, 33.5 S and 1.7 x 10(6) daltons, compared to 23 S and 1.0 x 10(6) dalton for SC5b-9. Because the molecular weight of the MAC is approximately two times greater than that of C5b-0 (800,000 daltons), the MAC is considered the dimer of C5b-9. Under specified conditions, the 33.5 S dimer could be converted to the 23 S monomer without dissociation of subunits. The MAC had the electron microscopic appearance and dimensions that are characteristic for the complement produced ultrastructural membrane lesions. SC5b-9 had a different ultrastructure that is dissimilar to the morphology of the lesions. The isolated MAC could be reincorporated into phospholipid bilayers and assumed on the surface of the resultant lipid vesicles the orientation and appearance of typical complement lesions.