tbuckley/cabot-search huggingface dataset:
Endothelial Cells Create a Stem Cell Niche in Glioblastoma by Providing NOTCH Ligands That Nurture Self-Renewal of Cancer Stem-Like Cells
Authors: Thant S. Zhu, Mark A. Costello, Caroline E. Talsma, Callie G. Flack, Jessica G. Crowley, Lisa L. Hamm, Xiaobing He, Shawn L. Hervey-Jumper, Jason A. Heth, Karin M. Muraszko, Francesco DiMeco, Angelo L. Vescovi, Xing Fan
Journal: Cancer Research (2011)

One important function of endothelial cells in glioblastoma multiforme (GBM) is to create a niche that helps promote self-renewal of cancer stem-like cells (CSLC). However, the underlying molecular mechanism for this endothelial function is not known. Since activation of NOTCH signaling has been found to be required for propagation of GBM CSLCs, we hypothesized that the GBM endothelium may provide the source of NOTCH ligands. Here, we report a corroboration of this concept with a demonstration that NOTCH ligands are expressed in endothelial cells adjacent to NESTIN and NOTCH receptor-positive cancer cells in primary GBMs. Coculturing human brain microvascular endothelial cells (hBMEC) or NOTCH ligand with GBM neurospheres promoted GBM cell growth and increased CSLC self-renewal. Notably, RNAi-mediated knockdown of NOTCH ligands in hBMECs abrogated their ability to induce CSLC self-renewal and GBM tumor growth, both in vitro and in vivo. Thus, our findings establish that NOTCH activation in GBM CSLCs is driven by juxtacrine signaling between tumor cells and their surrounding endothelial cells in the tumor microenvironment, suggesting that targeting both CSLCs and their niche may provide a novel strategy to deplete CSLCs and improve GBM treatment.
Facial expression of pain, empathy, evolution, and social learning
Authors: Amanda C. de C. Williams
Journal: Behavioral and Brain Sciences (2002)

The experience of pain appears to be associated, from early infancy and across pain stimuli, with a consistent facial expression in humans. A social function is proposed for this: the communication of pain and the need for help to observers, to whom information about danger is of value, and who may provide help within a kin or cooperative relationship. Some commentators have asserted that the evidence is insufficient to account for the consistency of the face, as judged by technical means or in the perceptions of observers, or that facial expression is epiphenomenal to a gross behavioural defensive response to pain. The major criticism is that it is unnecessary to invoke evolutionary mechanisms beyond the emergence of an unconditioned facial response to pain in neonates, subsequently shaped and maintained by instrumental and social reinforcement throughout life. These criticisms are addressed, acknowledging the need for further data to address some, and elaborating the areas in which evolutionary and operant mechanisms would predict different behavioural interactions, rather than acting synergistically. Several supportive commentaries propose extending evolutionarily-based hypotheses to sex differences, the complexities of others' responses within the social relationship, and the role of empathy. A number of commentators provided valuable suggestions for experimental paradigms or methodological issues. Overall, addressing these issues indicates the need for further conceptual development and for collection of data specifically in relation to these hypotheses.
Inflammation and the Paradox of Racial Differences in Dialysis Survival
Authors: Deidra C. Crews, Stephen M. Sozio, Yongmei Liu, Josef Coresh, Neil R. Powe
Journal: Journal of the American Society of Nephrology (2011)

African Americans experience a higher mortality rate and an excess burden of ESRD compared with Caucasians in the general population, but among those treated with dialysis, African Americans typically survive longer than Caucasians. We examined whether differences in inflammation may explain this paradox. We prospectively followed a national cohort of incident dialysis patients in 81 clinics for a median of 3 years (range 4 months to 9.5 years). Among 554 Caucasians and 262 African Americans, we did not detect a significant difference in median CRP between African Americans and Caucasians (3.4 versus 3.9 mg/L). Mortality was significantly lower for African Americans versus Caucasians (34% versus 56% at 5 years); the relative hazard was 0.7 (95% CI, 0.5 to 0.9) after adjusting for age, gender, dialysis modality, smoking, body mass index, diabetes, BP, cholesterol, cardiovascular disease, congestive heart failure, comorbid disease, hemoglobin, albumin, CRP, and IL-6. However, the risk varied by CRP tertile: the relative hazards for African Americans compared with Caucasians were 1.0 (95% CI, 0.7 to 1.4), 0.7 (95% CI, 0.4 to 1.3), and 0.5 (95% CI, 0.3 to 0.8) in the lowest, middle, and highest tertiles, respectively. We obtained similar results when we accounted for transplantation as a competing event, and we examined mortality across tertiles of IL-6. In summary, racial differences in survival among dialysis patients are not present at low levels of inflammation but are large at higher levels. Differences in inflammation may explain, in part, the racial paradox of ESRD survival.
Animal experiments and the doctor
Authors: A. Menache
Journal: Journal of the Royal Society of Medicine (2002)

Professor Vallance's editorial (June 2002 JRSM1) will be considered by most of your readers to be a well-balanced discussion on the use of animals in research. I too would agree with most of this article, were it not for the fact that I was trained as a veterinary surgeon who is acutely aware of the concept of species differences, not only between horses and canaries, but also between mice and men. However, most of my knowledge on the subject is the result of private research. I therefore believe that the reason ‘the medical profession as a whole has remained rather quiet’ is simply that most doctors have not made an in-depth study of the subject at hand. Most doctors do not know that the chimpanzees (our closest living relatives, with whom we share 98.4% of our DNA) are resistant to HIV, hepatitis B and common malaria. Similarly, most are not aware of the fact that humans are the only mammals who lack sialic acid on their cell surfaces, which represents a major obstacle to xenotransplantation (animal to human organ transplants), in addition to the other risks inherent in such transplants2.

The 3 Rs approach (replacement, reduction and refinement) is already out of date. This approach represents the old science of empiricism, based largely on experimentation and observation. The past 15-20 years have produced something of a scientific revolution, in terms of exact science. Is it really still necessary to perform toxic risk assessment on rodents and dogs, when we can observe the damaging effects of a chemical substance in human cell culture, at the molecular level?

The elucidation of the human genome clearly underlines the physiological differences between human individuals, let alone those between humans and animals. The way forward is individualized medicine, where patients will receive medication based on their genetic profile, thereby reducing the risk of adverse drug reactions which now rank as the fourth leading cause of death in western hospitals3. It should of course be noted that the medical drugs which are responsible for this virtual epidemic of adverse drug reactions were all thoroughly tested on laboratory animals, as is required by law. Does this sad statistic not say something about our regulatory system?
Chloride ions and the endothelium: their role in adrenoceptor-mediated vasoconstriction
Authors: M Alexander
Journal: Cardiovascular Research (2000)

See article by Tabrizchi and Duggan[1] ( pages 393 -guanylate cyclase, increasing cGMP levels, which causes a 401) in this issue.reduction in intracellular calcium and in turn causes smooth muscle relaxation [13].This report by Tabrizchi and Duggan [1] representsThe endothelium is also responsible for vasoconstriction another link in the continuing effort to evaluate factors induced by substances such as the a -adrenoceptor agon-1 NO is the endogenous activator of the soluble form of aortic contractions and it was found, that in the presence of L-NAME, there was an increase in tension in the aortic rings from the normotensive rats but a lack of effect in
Mechanisms of Gamma Oscillations
Authors: György Buzsáki, Xiao-Jing Wang
Journal: Annual Review of Neuroscience (2012)

Gamma rhythms are commonly observed in many brain regions during both waking and sleep states, yet their functions and mechanisms remain a matter of debate. Here we review the cellular and synaptic mechanisms underlying gamma oscillations and outline empirical questions and controversial conceptual issues. Our main points are as follows: First, gamma-band rhythmogenesis is inextricably tied to perisomatic inhibition. Second, gamma oscillations are short-lived and typically emerge from the coordinated interaction of excitation and inhibition, which can be detected as local field potentials. Third, gamma rhythm typically concurs with irregular firing of single neurons, and the network frequency of gamma oscillations varies extensively depending on the underlying mechanism. To document gamma oscillations, efforts should be made to distinguish them from mere increases of gamma-band power and/or increased spiking activity. Fourth, the magnitude of gamma oscillation is modulated by slower rhythms. Such cross-frequency coupling may serve to couple active patches of cortical circuits. Because of their ubiquitous nature and strong correlation with the "operational modes" of local circuits, gamma oscillations continue to provide important clues about neuronal population dynamics in health and disease.
ST segment mapping and infarct size
Authors: M Janse
Journal: Cardiovascular Research (2000)

Following the pioneering studies of Julian [1] and Lown and coworkers [2], demonstrating that ventricular fibrillation is common in patients with acute ischaemia, with and without infarction, and that it can be treated, coronary care units were installed in many medical centres, and attempts were made to hospitalise patients with acute ischaemic attacks as early as possible. As Professor Shillingford writes in this issue [3], the introduction of the coronary care unit offered the possibility to study patients who developed a myocardial infarction in a variety of ways. Pelides et al. [4] reported on nine patients ‘who had sustained an acute myocardial infarction within 72 hours’ in whom the administration of the beta-adrenergic blocker practolol reduced precordial ST segment elevation, which was interpreted as a reduction in the extent and severity of ischaemia.

The background for this 1972 study formed experimental studies by Maroko et al. in 1971 [5]. In this paper, it was stated: ‘Of greatest interest, from the clinical point of view, is the finding that the severity and extent of myocardial ischemic injury resulting from coronary occlusion could be radically altered not only by pretreatment of the animal but also by an appropriate intervention as late as 3 hours after the coronary occlusion’ [5]. In that study, propranolol administered 3 h after coronary artery occlusion reduced average ST elevation from 7.6 to 4.9 mV.

In the 1970s, a great many experimental studies were performed with the aim of reducing infarct size by a variety of means ranging from beta-blockers, nitroglycerin, mannitol, glucose-insulin-potassium infusion, hyaluronidase, hydrocortison and cobra venom (see [6,7]). In most of these studies ischaemic damage was determined by summation of ST segment elevation recorded at a number of epicardial sites. The precise mechanism of ST segment changes were unknown at …
Intracellular localization of tyrosine kinase substrates beneath crosslinked surface immunoglobulins in B cells.
Authors: S Takagi, M Daibata, T J Last, R E Humphreys, D C Parker, T Sairenji
Journal: The Journal of Experimental Medicine (1991)

Crosslinking of surface immunoglobulins (sIg) in B cells led to the accumulation of submembranal phosphotyrosine, which was followed morphologically with the PY20 antiphosphotyrosine monoclonal antibody. Phosphotyrosine was not detected before sIg crosslinking. After sIg crosslinking, phosphotyrosine-containing proteins were redistributed from scattered small clusters near the plasma membrane to a juxtanuclear region, where immunofluorescent staining decreased with time. Double immunofluorescent staining of individual cells showed accumulation of phosphotyrosine beneath crosslinked sIg molecules at the cell surface. The sIg molecules were subsequently internalized more rapidly than the phosphotyrosine-containing molecules were redistributed. Genistein, a protein tyrosine kinase (PTK) inhibitor, blocked intracellular tyrosine phosphorylations but not cell surface patching of crosslinked sIg. When polyacrylamide beads coated with anti-Ig antibodies were added to the cells, intracellular tyrosine phosphorylation occurred beneath the regions of contact with the beads. This study provides an independent line of evidence confirming recent biochemical experiments that show that crosslinking of the antigen receptor induces PTK activity in B cells, and that components of the newly described sIg complex are among the PTK substrates. The surprising finding that the bulk of the induced phosphotyrosine remains associated with crosslinked sIg for many minutes suggests a role for complex local protein interactions in phosphotyrosine-mediated signal transduction through the antigen receptor of B cells.
Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer
Authors: J-P. Machiels, C. Sempoux, P. Scalliet, J-C. Coche, Y. Humblet, E. Van Cutsem, J. Kerger, J-L. Canon, M. Peeters, S. Aydin, S. Laurent, A. Kartheuser, B. Coster, S. Roels, J-F. Daisne, B. Honhon, L. Duck, C. Kirkove, M-A. Bonny, K. Haustermans
Journal: Annals of Oncology (2007)
Regulation of K+ channels in cardiac myocytes by free fatty acids.
Authors: D Kim, R A Duff
Journal: Circulation Research (1990)

Using rat ventricular cells, we studied the actions of free fatty acids and their ability to modulate the ATP-sensitive K+ channel and to activate a new type of ATP-insensitive K+ channel previously identified in rat atrial cells. Perfusion of the cytoplasmic face of the membrane with unsaturated fatty acids (10-50 microM) such as arachidonic, linoleic, and eicosatrienoic acids inhibited the ATP-sensitive K+ channel almost completely; lysophospholipids also markedly inhibited this channel. Inhibition was due to decreases in the frequency and the burst duration of channel openings. Arachidonic acid activated the ATP-insensitive K+ channel with an outwardly rectifying property. Since the level of free fatty acids rises after longer periods of ischemia, we speculate that the ATP-insensitive K+ channel contributes to the late or secondary phase of extracellular K+ accumulation.
Naproxen-induced generalized bullous fixed drug eruption
Authors: T. Leivo, H. Heikkila
Journal: British Journal of Dermatology (2004)

Journal Article Naproxen‐induced generalized bullous fixed drug eruption Get access T. Leivo, T. Leivo Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, 00250 Helsinki, Finland Tomi Leivo, Melkonkatu 1 B S1, 00210 Helsinki, Finland E‐mail: tomi.leivo@hus.fi Search for other works by this author on: Oxford Academic Google Scholar H. Heikkilä H. Heikkilä Department of Dermatology, Helsinki University Central Hospital, Meilahdentie 2, 00250 Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 1, 1 July 2004, Page 232, https://doi.org/10.1111/j.1365-2133.2004.05988.x Published: 01 July 2004
Calcium, Vitamin D, and the Occurrence of Colorectal Cancer Among Women
Authors: M E Martínez, E L Giovannucci, G A Colditz, M J Stampfer, D J Hunter, F E Speizer, A Wing, W C Willett
Journal: JNCI Journal of the National Cancer Institute (1996)

Despite evidence from animal studies for a protective effect of higher calcium and possibly vitamin D intake against colorectal cancer, epidemiologic studies have been inconclusive.We investigated the associations between the intake of calcium and vitamin D and the occurrence of colorectal cancer.In a prospective study, 89 448 female registered nurses who were free of cancer responded to a mailed, semiquantitative food-frequency questionnaire in 1980; dietary information was updated in 1984 and 1986. Through 1992, 501 incident cases of colorectal cancer (396 colon and 105 rectal cancers) were documented. As measures of exposure, we used nutrient intake in 1980 and also two measures of long-term intake on the basis of the three questionnaires: the average of intakes from the three questionnaires and consistent intakes, which were defined as high if women were in the upper tertile on all questionnaires and low if they were in the lower tertile on all questionnaires. To further characterize long-term intake, we conducted analyses excluding women who reported a change in their consumption of milk (primary source of calcium and vitamin D) in the 10 years prior to 1980. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the lowest quintile of intake as a reference. The Mantel extension test was used to evaluate linear trends across the categories of nutrient intake. In multivariate analyses, the trends were tested with use of the medians of the intake as a continuous variable in the logistic model. The P values for the trends were two-sided.On the basis of the data from the 1980 questionnaire alone, the multivariate RR for colorectal cancer for women in the upper versus the lower quintile were 0.80 (95% CI = 0.60-1.07) for dietary calcium, 0.84 (95% CI = 0.63-1.13) for dietary vitamin D (from foods only), and 0.88 (95% CI = 0.66-1.16) for total vitamin D (from foods and supplements). After the exclusion of women who reported a change in their milk intake, the RRs for colorectal cancer for the highest versus the lowest categories of average intake were 0.74 (95% CI = 0.36-1.50) for dietary calcium, 0.72 (95% CI = 0.34-1.54) for dietary vitamin D, and 0.42 (95% CI = 0.19-0.91) for total vitamin D. The corresponding RRs for the consistency analyses were 0.70 (95% CI = 0.35-1.39) for dietary calcium, 0.59 (95% CI = 0.30- 1.16) for dietary vitamin D, and 0.33 (95% CI = 0.16-0.70) for total vitamin D.These findings do not support a substantial inverse association between calcium intake and risk of colorectal cancer, but an inverse association between intake of total vitamin D and risk of colorectal cancer was suggested.Available evidence does not warrant an increase in calcium intake to prevent colon cancer, but longer-term studies of both calcium and especially vitamin D in relation to colorectal cancer risk are needed.
Impact of anatomical location on barrier recovery, surface pH and stratum corneum hydration after acute barrier disruption
Authors: J.W. Fluhr, H. Dickel, O. Kuss, I. Weyher, T.L. Diepgen, E. Berardesca
Journal: British Journal of Dermatology (2002)

It is not known whether distinct anatomical locations will respond with different recovery rates following acute barrier challenges.To investigate whether barrier parameters differ at five body sites during recovery from acute disruption.Acute barrier disruption was achieved by tape stripping and by acetone extraction of stratum corneum lipids. Transepidermal water loss (to assess barrier function), capacitance (for stratum corneum hydration) and skin surface pH were measured at each of five different body sites in 14 human volunteers. Individual measurements were obtained every 24 h for 96 h.Lipid-rich skin areas (e.g. the forehead) were the most vulnerable to barrier disruption by either method. While acetone treatment affected barrier function and decreased stratum corneum hydration, tape stripping similarly altered barrier function but increased capacitance values. Although the effect of barrier disruption on surface pH appeared to vary with location, no significant pattern of variation emerged. Independent of the method used for barrier disruption, the pH normalized within 96 h.Skin at different body sites shows distinct patterns of barrier recovery that are likely to be related to structural and physiological differences. Therefore, 'anatomically specific' regimens appear possible and relevant for the treatment of cutaneous disorders. In addition, adequate statistical analyses are essential to detect real differences in barrier recovery parameters.
90 Y-labelled anti-CD22 epratuzumab tetraxetan in adults with refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia: a phase 1 dose-escalation study
Authors: Patrice Chevallier, Thomas Eugene, Nelly Robillard, Françoise Isnard, Franck Nicolini, Martine Escoffre-Barbe, Françoise Huguet, Mathilde Hunault, Antoine Marcais, Joelle Gaschet, Michel Cherel, Thierry Guillaume, Jacques Delaunay, Pierre Peterlin, Marion Eveillard, Xavier Thomas, Norbert Ifrah, Simona Lapusan, Caroline Bodet-Milin, Jacques Barbet, Alain Faivre-Chauvet, Ludovic Ferrer, Marie C Bene, Claire Le Houerou, David M Goldenberg, William A Wegener, Françoise Kraeber-Bodéré
Journal: The Lancet Haematology (2015)
Pregnancy and Adrenocortical Function: Endocrine Studies of Pregnancy Occurring in Two Adrenal-Deficient Women1
Authors: A. Gorman Hills, Eleanor H. Venning, F. Curtis Dohan, George D. Webster, Edwin M. Richardson
Journal: Journal of Clinical Investigation (1954)

It has been suggested by jailer and Knowlton(1) that when adrenal-deficient women become pregnant, they exhibit "simulated adrenal cortical activity" attributable to an extra-adrenal source of "adrenal cortical-like" hormone.Observations which can be interpreted as lending support to this view may be summarized as follows:1. Pregnancy has been reported to prolong the survival of adrenalectomized animals (24).2. Urinary 17-ketosteroid elimination (as estimated by the Zimmermann reaction) rises during the latter months of pregnancy in patients with Addison's disease (1, 5, 6) as well as in normal women (7).3. Urinary excretion of neutral reducing lipids rose to the normal range late in pregnancy in one patient with Addison's disease (1).4. A decrease of circulating eosinophils four hours following the injection either of epinephrin or of corticotrophin was observed on three occa- sions in one Addisonian patient during pregancy and not thereafter (1).The occurrence of pregnancy in two women rendered adrenal-deficient by surgery because of severe hypertensive disease has provided an op- portunity to conduct certain studies, reported in this communication, which bear upon the question.