tbuckley/cabot-search huggingface dataset:
Induction of Nitric Oxide Synthase and Dual Effects of Nitric Oxide and Cyclooxygenase Products in Regulation of Arterial Contraction in Human Septic Shock
Authors: J. C. Stoclet, M. C. Martínez, P. Ohlmann, S. Chasserot, C. Schott, A. L. Kleschyov, F. Schneider, R. Andriantsitohaina
Journal: Circulation (1999)

Background —The role of endogenous nitric oxide (NO) and cyclooxygenase metabolites was investigated in contractile responses of small omental arteries from patients with hyperdynamic septic shock. Methods and Results —Expression of inducible NO synthase (immunostaining) and a high but variable level of NO production (NO spin trapping) was detected in arteries from patients with septic shock. In these vessels, ex vivo contractile responses to the thromboxane A 2 analogue U46619 and to low concentrations of norepinephrine (NE) (up to 10 μmol/L) were not significantly different from controls. However, higher concentrations of NE caused pronounced fading of contraction in septic but not in nonseptic arteries. Exposure to either the NO synthase inhibitor N G -nitro- l -arginine methyl ester or the cyclooxygenase inhibitor indomethacin had no effect in control vessels. However, both inhibitors increased the response to the contractile effects of the 2 agonists only in patients with septic shock. In contrast to N G -nitro- l -arginine methyl ester, which decreased the threshold concentration of the fading effect of NE, indomethacin abolished this effect in arteries from septic patients. Conclusions —These results provide direct evidence for the induction of NO synthase in small arteries from patients with septic shock. They suggest that in these arteries, increased production of NO, in conjunction with vasodilatory cyclooxygenase metabolites, contributes to counteract hyperreactivity to agonists and decreases the cyclooxygenase product–mediated pronounced fading of contraction caused by a high concentration of NE.
Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality
Authors: Issa F. Khouri, Rima M. Saliba, Sergio A. Giralt, Ming-Sheng Lee, Grace-Julia Okoroji, Fredrick B. Hagemeister, Martin Korbling, Anas Younes, Cindy Ippoliti, James L. Gajewski, Peter McLaughlin, Paolo Anderlini, Michele L. Donato, Fernando F. Cabanillas, Richard E. Champlin
Journal: Blood (2001)
Late quantitative angiographic results after NIR stent use: results from the NIRVANA randomized trial end registries
Authors: A.J. Lansky, J.J. Popma, R. Mehran, J.F. Saucedo, A.S. Abizaid, C. O'Shaughnessy, J.B. Hermiller, D. Cutlip, R.E. Kuntz, D.S. Baim, M.B. Leon
Journal: Journal of the American College of Cardiology (1998)
Evolution of Mechanical Ventilation in Response to Clinical Research
Authors: Andrés Esteban, Niall D. Ferguson, Maureen O. Meade, Fernando Frutos-Vivar, Carlos Apezteguia, Laurent Brochard, Konstantinos Raymondos, Nicolas Nin, Javier Hurtado, Vinko Tomicic, Marco González, José Elizalde, Peter Nightingale, Fekri Abroug, Paolo Pelosi, Yaseen Arabi, Rui Moreno, Manuel Jibaja, Gabriel D'Empaire, Fredi Sandi, Dimitros Matamis, Ana María Montañez, Antonio Anzueto
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Recent literature in mechanical ventilation includes strong evidence from randomized trials. Little information is available regarding the influence of these trials on usual clinical practice.To describe current mechanical ventilation practices and to assess the influence of interval randomized trials when compared with findings from a 1998 cohort.A prospective international observational cohort study, with a nested comparative study performed in 349 intensive care units in 23 countries. We enrolled 4,968 consecutive patients receiving mechanical ventilation over a 1-month period. We recorded demographics and daily data related to mechanical ventilation for the duration of ventilation. We systematically reviewed the literature and developed 11 practice-change hypotheses for the comparative cohort study before seeing these results. In assessing practice changes, we only compared data from the 107 intensive care units (1,675 patients) that also participated in the 1998 cohort (1,383 patients).In 2004 compared with 1998, the use of noninvasive ventilation increased (11.1 vs. 4.4%, P < 0.001). Among patients with acute respiratory distress syndrome, tidal volumes decreased (7.4 vs. 9.1 ml/kg, P < 0.001) and positive end-expiratory pressure levels increased slightly (8.7 vs. 7.7 cm H(2)O, P = 0.02). More patients were successfully extubated after their first attempt of spontaneous breathing (77 vs. 62%, P < 0.001). Use of synchronized intermittent mandatory ventilation fell dramatically (1.6 vs. 11%, P < 0.001). Observations confirmed 10 of our 11 practice-change hypotheses.The strong concordance of predicted and observed practice changes suggests that randomized trial results have advanced mechanical ventilation practices internationally.
Neuroleptic-induced supersensitivity psychosis
Authors: G Chouinard, B D Jones, L Annable
Journal: American Journal of Psychiatry (1978)

drops from neurologic disease, pilocarpine, a parasympathomimetic agent, is safe and reliable. It causes ·constriction of the iris sphincter unless atropine or an·other postsynaptic blocker, such as tropicamide, the substance involved in this case, has been used. Physostigmine salicylate (Antilirium) was not used, · but it is effective in treating anticholinergic intoxica.' tion when administered intramuscularly (l mg repeated in 15-20 minutes if necessary). In Ms. A's case, the anticholinergic effects of chlorpromazine, amitriptyline, scopolamine (Sominex) (0), and tropicamide were probably additive. Although her disorientation cleared rapidly, Ms. A maintained that her hallucinations persisted during her 2-week hospitalization. However, it is difficult to know : whether this was actually the case. Given the previous diagnosis of Munch~lUsen syndrome and her unusual willingness to assume the psychiatric patient role as well as the medical-surgical patient role, it is not unlikely that she was attempting to prolong her hospitalization.
Human Placental Lactogen: Studies of Its Acute Metabolic Effects and Disposition in Normal Man*
Authors: Paul Beck, William H. Daughaday
Journal: Journal of Clinical Investigation (1967)

The acute metabolic effects and disposition of human placental lactogen (HPL) have been studied in 15 men and 8 women during continuous intravenous infusions. The mean plasma half-life, metabolic pool size, and turnover rate of HPL are comparable to the values previously reported for human growth hormone (HGH). From the data presented, we calculate that the placenta secretes approximately 290 mg HPL daily at term. After 12-hour infusions of HPL in physiologic amounts, impairment of glucose tolerance despite increased plasma insulin responses to glucose was observed in 7 of 8 subjects tested. However, HPL, unlike HGH, did not produce significant changes in blood glucose, plasma insulin, or plasma free fatty acid concentrations in fasting subjects before glucose administration or in carbohydrate tolerance or plasma insulin responses to glucose during 5-hour infusions. These findings are compatible with the thesis that HPL is a physiologic antagonist to insulin during pregnancy.
Role of the Cdc25A phosphatase in human breast cancer
Authors: M. Giulia Cangi, Barry Cukor, Peggy Soung, Sabina Signoretti, Gilberto Moreira, Moksha Ranashinge, Blake Cady, Michele Pagano, Massimo Loda
Journal: Journal of Clinical Investigation (2000)

The phosphatase Cdc25A plays an important role in cell cycle regulation by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases, and it has been shown to transform diploid murine fibroblasts in cooperation with activated Ras. Here we show that Cdc25A is overexpressed in primary breast tumors and that such overexpression is correlated with higher levels of cyclin-dependent kinase 2 (Cdk2) enzymatic activity in vivo. Furthermore, in the breast cancer cell line MCF-7, Cdc25A activity is necessary for both the activation of Cdk2 and the subsequent induction of S-phase entry. Finally, in a series of small (< 1 cm) breast carcinomas, overexpression of Cdc25A was found in 47% of patients and was associated with poor survival. These data suggest that overexpression of Cdc25A contributes to the biological behavior of primary breast tumors and that both Cdc25A and Cdk2 are suitable therapeutic targets in early-stage breast cancer.
Retro-retinoids in regulated cell growth and death.
Authors: M J O'Connell, R Chua, B Hoyos, J Buck, Y Chen, F Derguini, U Hämmerling
Journal: The Journal of Experimental Medicine (1996)

Vitamin A serves as a prohormone from which three classes of active metabolites are derived: the aldehydes, the carboxylic acids, and the retro-retinoids. Although these three classes are united under the rubric of signal transduction, they act by different molecular mechanisms: the 11-cis-retinaldehydes combine with opsin to form the universal visual pigments and the retinoic acids form ligands for transcription factors, whereas the retro-retinoids, as shown here, intersect with signal transduction at a cytoplasmic or membrane site. The retro-retinoid, anhydroretinol (AR), has long been known to act as a growth inhibitor in lymphocytes, whereas 14-hydroxy-4,14-retro-retinol (14-HRR) is required for normal lymphocyte proliferation. A mutually reversible relationship exists between these two retro-retinoids as one can reverse the effects of the other when given in pharmacological doses. The common explanation for reversible inhibition is competition for a shared receptor. We now provide evidence that when AR is given to T cells unmitigated by 14-HRR, rapid cell death can occur. The circumstances are closely related to nonclassical forms of apoptosis: within 2 h of AR administration the T cells undergo widespread morphological changes, notably surface blebbing and ballooning and, inevitably, bursting. In contrast, nuclear changes are comparatively mild, as indicated by absence of chromatin condensation and overt DNA cleavage to discrete nucleosomal fragments, although DNA nicks are readily discernible by terminal deoxynucleotidyl transferase assay. What further distinguishes the AR-induced form of apoptosis from classical ones is a lack of requirements of messenger RNA and protein synthesis, suggesting that the events leading to cell death are primarily initiated and play themselves out in the cytoplasm. This view is further reinforced by the finding that herbimycin A can prevent the onset of programmed cell death. The importance of our findings is that they strongly suggest a second messenger role for vitamin A metabolites in the cytoplasmic realm that has not been seen previously. These findings are entirely compatible with a general notion that in a cell requiring multiple coordinated signals for survival, the provision of an unbalanced signal can initiate programmed cell death. Collectively, our data also challenge the paradigm that retinoids (outside vision) solely mediate their function via the steroid/ retinoic acid receptor family of nuclear transcription factors. Instead, a mode of action in the cytoplasmic realm akin to one attributed to other small lipophilic second messenger molecules, such as diacyl glycerol or ceramide, may apply to retro-retinoids.
Temporal relationships between episodes of non-cardiac chest pain and abnormal oesophageal function.
Authors: H G Lam, R Breumelhof, G P van Berge Henegouwen, A J Smout
Journal: Gut (1994)

Analysis of the association between symptoms and abnormal oesophageal function is a central part of 24 hour oesophageal pressure and pH recording in patients with non-cardiac chest pain. Such studies have used different time windows including a period after the onset of pain. Since stress and pain can induce oesophageal motor abnormalities and transient lower oesophageal sphincter relaxations, a proportion of the motor abnormalities and the reflux episodes observed after the onset of pain may be a consequence rather than the cause of that pain. This study aimed to assess this possibility in patients with chest pain that was presumed to be of oesophageal origin by comparing the results of analysis using time windows before and after the onset of pain. Forty eight patients experienced a total of 166 spontaneous chest pain episodes during 24 hour ambulatory monitoring. A time window beginning two minutes before and ending at the onset of pain (-2/0) was compared with a window beginning at the onset of pain and ending two minutes afterwards (0/+2). The percentage of episodes related to reflux, abnormal oesophageal motility, or neither were 22.9%, 24.7%, and 52.4% in the -2/0 time window and 9.0%, 22.3%, and 68.7% in the 0/+2 time window, respectively. However, 11 of the 37 episodes associated with abnormal motility in the 0/+2 time window were preceded by a reflux episode, and 19 of these 37 episodes had abnormal motility in the -2/0 time window. Consequently, in only seven of the 166 chest pain episodes (4.2%) in two patients were the findings consistent with secondary oesophageal motor disorders provoked by pain. Likewise, only six of the 166 chest pain episodes (3.6%) were consistent with reflux provoked by pain. These findings indicate that in patients with non-cardiac chest pain, gastro-oesophageal reflux and oesophageal motor abnormalities are rarely a consequence of the pain.
Protein Expression and Functional Analysis of the FHIT Gene in Human Tumor Cells
Authors: G A Otterson, G H Xiao, J Geradts, F Jin, W D Chen, W Niklinska, F J Kaye, R S Yeung
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The fragile histidine triad (FHIT) gene at chromosome 3p14.2 has been proposed to be a candidate tumor suppressor gene in human cancers. To test whether FHIT exhibits the functional properties of a tumor suppressor gene, we studied the expression of its protein (pFHIT) in human carcinoma cells and examined the ability of FHIT to inhibit the neoplastic phenotype of cancer cells. Methods: Subcellular localization and patterns of protein expression in tumor cells were determined by immunohistochemical analysis and immunoblotting with the use of polyclonal antipFHIT antisera. In tumor cells with undetectable pFHIT, we examined the effect of recombinant pFHIT expression on morphology, growth rate, colony formation, and in vivo tumor formation. Results: We demonstrated that pFHIT is a cytoplasmic 17-kd polypeptide whose expression could not be detected in 30 of 52 human carcinoma cell lines tested. We observed, however, that the stable overexpression of pFHIT did not alter cell morphology, inhibit colony formation, or inhibit cell proliferation in vitro. Furthermore, overexpression of pFHIT did not lead to altered cell cycle kinetics in dividing cells. The in vivo tumorigenicity of a tumor cell line that expressed high levels of recombinant pFHIT was equivalent to that of control transfectants and of parental cells. Conclusions: These results suggest that the replacement of pFHIT in human carcinoma cells does not suppress tumor cell growth and that this protein may be involved in tumorigenesis in ways that are distinct from the "classic" tumor suppressor paradigm.
The course of allergen-induced leukocyte infiltration in human and experimental asthma
Authors: Marek Lommatzsch, Peter Julius, Michael Kuepper, Holger Garn, Kai Bratke, Sabrina Irmscher, Werner Luttmann, Harald Renz, Armin Braun, J. Christian Virchow
Journal: Journal of Allergy and Clinical Immunology (2006)
Birth date and birth place effects in National Hockey League draftees 2000-2005: comments on Baker and Logan (2007)
Authors: David J Hancock, Diane M Ste-Marie, Bradley W Young
Journal: British Journal of Sports Medicine (2008)

Researchers who study the relative age effect (RAE) have stated that, within a given cohort, individuals who are relatively older tend to be over-represented at elite levels within sport. This RAE has been illustrated in hockey,1 soccer,2 and baseball,3 to name a few.

Recently, Baker and Logan4 conducted an analysis on the birth dates of players drafted to the National Hockey League (NHL) between 2000 and 2005. The results led them to conclude that a RAE existed, as relatively older players were over-represented in the NHL drafts. After appraising their contribution, we feel that there are three key points to be reconsidered. These considerations do not disqualify the notion that a RAE exists in NHL draftees; however, they compel one to re-examine study design issues and the interpretation of results.

The first point for reconsideration concerns the birth quartiles used by the authors. Specifically, Baker and Logan4 divided their sample into quartiles (Q) based on the calendar year for US and Canadian hockey, which is 1 January to 31 December (Q1  =  January to March, Q2  =  April to June, Q3  =  July to September, Q4  =  October to December). The NHL draft calendar, however, runs from 16 September to 15 September. For example, in the 2008 NHL draft, first-year eligible players were born between 16 September 1989 and 15 September 1990. Thus, the relatively oldest players in an NHL draft cohort are born on …
Abdominal Aortic Aneurysm: A Study of One Hundred and Two Cases
Authors: J. EARLE ESTES
Journal: Circulation (1950)

Data were compiled from the records of 101 cases of abdominal aortic aneurysm, almost all of which were due to arteriosclerosis. These records were selected only when there was unequivocal evidence of aneurysm, and cases of true dissecting aneurysm were not included. The data were studied primarily in regard to prognosis of this condition but in addition, all clinical manifestations of abdominal aortic aneurysm were reviewed.
Targeting mitochondria to overcome conventional and bortezomib/proteasome inhibitor PS-341 resistance in multiple myeloma (MM) cells
Authors: Dharminder Chauhan, Guilan Li, Klaus Podar, Teru Hideshima, Constantine Mitsiades, Robert Schlossman, Nikhil Munshi, Paul Richardson, Finbarr E. Cotter, Kenneth C. Anderson
Journal: Blood (2004)
Radiotherapy Increases the Permissiveness of Established Mammary Tumors to Rejection by Immunomodulatory Antibodies
Authors: Inge Verbrugge, Jim Hagekyriakou, Leslie L. Sharp, Mara Galli, Alison West, Nicole M. McLaughlin, Hélène Duret, Hideo Yagita, Ricky W. Johnstone, Mark J. Smyth, Nicole M. Haynes
Journal: Cancer Research (2012)

It is becoming increasingly evident that radiotherapy may benefit from coincident or subsequent immunotherapy. In this study, we examined whether the antitumor effects of radiotherapy, in established triple-negative breast tumors could be enhanced with combinations of clinically relevant monoclonal antibodies (mAb), designed to stimulate immunity [anti-(α)-CD137, α-CD40] or relieve immunosuppression [α-programmed death (PD)-1]. While the concomitant targeting of the costimulatory molecules CD137 and CD40 enhanced the antitumor effects of radiotherapy and promoted the rejection of subcutaneous BALB/c-derived 4T1.2 tumors, this novel combination was noncurative in mice bearing established C57BL/6-derived AT-3 tumors. We identified PD-1 signaling within the AT-3 tumors as a critical limiting factor to the therapeutic efficacy of α-CD137 therapy, alone and in combination with radiotherapy. Strikingly, all mice bearing established orthotopic AT-3 mammary tumors were cured when α-CD137 and α-PD-1 mAbs were combined with single- or low-dose fractionated radiotherapy. CD8+ T cells were essential for curative responses to this combinatorial regime. Interestingly, CD137 expression on tumor-associated CD8+ T cells was largely restricted to a subset that highly expressed PD-1. These CD137+PD-1High CD8+ T cells, persisted in irradiated AT-3 tumors, expressed Tim-3, granzyme B and Ki67 and produced IFN-γ ex vivo in response to phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation. Notably, radiotherapy did not deplete, but enriched tumors of functionally active, tumor-specific effector cells. Collectively, these data show that concomitant targeting of immunostimulatory and inhibitory checkpoints with immunomodulatory mAbs can enhance the curative capacity of radiotherapy in established breast malignancy.
Women's views on the impact of operative delivery in the second stage of labour: qualitative interview study
Authors: D. J Murphy
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To obtain the views of women on the impact of operative delivery in the second stage of labour. <b>Design</b> Qualitative interview study. <b>Setting</b> Two urban teaching hospitals in the United Kingdom. <b>Participants</b> Purposive sample of 27 women who had undergone operative delivery in the second stage of labour between January 2000 and January 2002. <b>Key themes</b> Preparation for birth, understandings of the indications for operative delivery, and explanation or debriefing after birth. <b>Results</b> The women felt unprepared for operative delivery and thought that their birth plan or antenatal classes had not catered adequately for this event. They emphasised the importance of maintaining an open mind about the management of labour. They had difficulty understanding the need for operative delivery despite a review by medical and midwifery staff before discharge. Operative delivery had a noticeable impact on women9s views about future pregnancy and delivery. <b>Conclusions</b> Women consider postnatal debriefing and medical review important deficiencies in current care. Those who experienced operative delivery in the second stage of labour would welcome the opportunity to have a later review of their intrapartum care, physical recovery, and management of future pregnancies.
Précis of <i>The Origin of Concepts</i>
Authors: Susan Carey
Journal: Behavioral and Brain Sciences (2011)

A theory of conceptual development must specify the innate representational primitives, must characterize the ways in which the initial state differs from the adult state, and must characterize the processes through which one is transformed into the other. The Origin of Concepts (henceforth TOOC) defends three theses. With respect to the initial state, the innate stock of primitives is not limited to sensory, perceptual, or sensorimotor representations; rather, there are also innate conceptual representations. With respect to developmental change, conceptual development consists of episodes of qualitative change, resulting in systems of representation that are more powerful than, and sometimes incommensurable with, those from which they are built. With respect to a learning mechanism that achieves conceptual discontinuity, I offer Quinian bootstrapping. TOOC concludes with a discussion of how an understanding of conceptual development constrains a theory of concepts.
Elective Primary Cesarean Delivery
Authors: Howard Minkoff, Frank A. Chervenak
Journal: New England Journal of Medicine (2003)

Some women would prefer an elective cesarean delivery to labor. The authors of this Sounding Board article review the arguments for and against elective cesarean delivery. They conclude that the available data do not support the routine recommendation of this approach but that they do support a physician's acceding to a request for cesarean delivery made by an informed patient.