tbuckley/cabot-search huggingface dataset:
Transplantation of the heart and both lungs: I. Historical review
Authors: D. K. C. Cooper
Journal: Thorax (1969)

Transplantation of the heart and both lungs is being considered as a clinical possibility in several surgical centres today. This paper reviews the experimental development of surgical techniques in this field. In the 1940s Demikhov in the U.S.S.R. succeeded in developing a technique by which he could carry out cardiopulmonary transplantation without the use of any artificial means of recipient support during the procedure. He obtained survivors for up to six days; late deaths occurred mainly from pulmonary complications. The techniques and results of subsequent workers using hypothermia or pump-oxygenator support are reviewed. Recent work has focused on the problem of the return of spontaneous respiration following denervation of the lungs which, of necessity, occurs during this procedure.
Management and control of asthma as assessed by actual/best function and corticosteroid use 1980-1993/4
Authors: CK Connolly, SM Alcock, RJ Prescott
Journal: European Respiratory Journal (1998)

This study aimed to determine whether the changes in practice in the management of asthma since the early 1980s have improved standards (as assessed by higher actual/best function) and reduced the need for oral corticosteroids. All asthmatic outpatients were reviewed in 1980, 1983, 1988/89 and 1993/94. Therapeutic step, defined by suppressive medication alone, actual and best peak expiratory flow (PEF) were recorded. Cohorts from 1980, 1983 and 1988/89 were identified in whom best function was established on all subsequent occasions. Changes in practice demonstrated by cross-sectional review of all subjects were interpreted with the aid of longitudinal analysis of the cohorts. Attendance increased from 463 in 1980 to 772 in 1993/94. Between 1983 and 1993/94, the proportion maintained on inhaled corticosteroids increased from 49 to 84% with increased use of higher doses. Mean actual/best PEF rose from 80 to 87%, improving at each therapeutic step. The proportion needing rescue oral corticosteroids fell from 47 to 35% and maintenance oral corticosteroids from 20 to 9%. In the cohorts, there was a similar reduction in use of rescue corticosteroids, but not of maintenance oral corticosteroids. The study confirmed an increase in the use and dose of inhaled corticosteroids, and a better outcome at all treatment steps. The fall in the proportion of subjects dependent on oral corticosteroids was due to attrition, rather than weaning in later years.
Heart failure with preserved ejection fraction in patients with chronic obstructive pulmonary disease exacerbation is associated with poor long-term survival
Authors: Robert Marcun, Ivan Stankovic, Jerneja Farkas, Alja Vlahovic, Biljana Putnikovic, Sasa Kadivec, Mitja Kosnik, Alekandar Neskovic, Mitja Lainscak
Journal: European Respiratory Journal (2013)

Background: Diagnosing heart failure with preserved ejection fraction (HFPEF) in patients with chronic obstructive pulmonary disease (COPD) is difficult due to overlapping symptoms and signs. We sought to identify the prevalence and prognostic implications of HFPEF in patients hospitalized for COPD exacerbation.  Methods: A total of 119 consecutive patients (70±10 years, 68% men) with acute exacerbation of COPD were included in the study. The diagnosis of HFPEF was made according to the consensus statement of the European Society of Cardiology. Patients were followed for 22±9 months and all-cause mortality was analyzed.  Results: HFPEF was diagnosed in 23 (19%) patients, who were older (75±10 vs. 69±10 years; p=0.013), and more frequently had arterial hypertension (65 vs. 37%; p=0.018) and atrial fibrillation (48 vs. 8%; p  Conclusions: HFPEF was present in 19% of COPD patients and is associated with poor long-term survival.
Listeria monocytogenes-reactive T lymphocyte clones with cytolytic activity against infected target cells.
Authors: S H Kaufmann, E Hug, G De Libero
Journal: The Journal of Experimental Medicine (1986)

Lyt-2+ T cell clones were established from Listeria monocytogenes-infected mice. The clones secreted IFN-gamma after stimulation with spleen cells from L. monocytogenes-infected mice plus IL-2. Spleen cells from normal mice were not stimulatory. Furthermore, cloned T cells lysed L. monocytogenes-infected macrophages. Cytolysis was antigen-specific and H-2K-restricted. These findings suggest a role for specific cytotoxic T cells in the immune response to intracellular bacteria.
Nasal mucociliary transport in healthy subjects is slower when breathing dry air
Authors: B Salah, AT Dinh Xuan, JL Fouilladieu, A Lockhart, J Regnard
Journal: European Respiratory Journal (1988)

We assessed the effect of dry air (DA) nasal breathing on nasal clearance rate in healthy nonsmoking subjects. We measured saccharin nasal transit time (SNTT), an index of mucociliary clearance rate, in eleven normal subjects (six males, five females) breathing either room air (RA) or DA through the nose in random order on six different study days. On each study day, the trial was conducted at the same time, in the same nostril, using a patent airway. DA was breathed through a light-weight, tight-fitting, nasal mask (SEFAM, France) for 30 min and SNTT was then measured immediately. Saccharin (250 micrograms) was deposited on the anterior part of the inferior turbinate under visual control and saliva was swallowed every 30 s thereafter. SNTT was the time elapsed between deposition and first perception of saccharin taste. The group-average SNTT on DA was 18.5 +/- 8.6 min which was significantly longer than on RA (11.9 +/- 5.3 min). Our findings suggest that dry air breathing results in excessive water loss by the nasal mucosa, which may in turn reduce nasal mucociliary clearance rate through changes in the rheological properties or adhesiveness of nasal mucus and/or slowing of ciliary beating.
Commentary on "Influence of anthropometry on race performance in extreme endurance triathletes: World Challenge Deca Iron Triathlon 2006"
Authors: Christoph Josef Raschka
Journal: British Journal of Sports Medicine (2007)

In correlations of anthropometric data with performance, whether the investigated group is homogeneous or heterogeneous should be determined. A significantly positive relationship between body mass and running time can exist for a group of sprinters who …
Thalidomide in Total Therapy 2 Overcomes Inferior Prognosis of Myeloma with Low Expression of the Glucocorticoid Receptor Gene<i>NR3C1</i>
Authors: Christoph J. Heuck, Jackie Szymonifka, Emily Hansen, John D. Shaughnessy, Saad Z. Usmani, Frits van Rhee, Elias Anaissie, Bijay Nair, Sarah Waheed, Yazan Alsayed, Nathan Petty, Clyde Bailey, Joshua Epstein, Antje Hoering, John Crowley, Bart Barlogie
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Because dexamethasone remains a key component of myeloma therapy, we wished to examine the impact of baseline and relapse expression levels of the glucocorticoid receptor gene NR3C1 on survival outcomes in the context of treatment with or without thalidomide. Experimental Design: We investigated the clinical impact of gene expression profiling (GEP)–derived expression levels of NR3C1 in 351 patients with GEP data available at baseline and in 130 with data available at relapse, among 668 subjects accrued to total therapy 2 (TT2). Results: Low NR3C1 expression levels had a negative impact on progression-free survival (PFS; HR, 1.47; P = 0.030) and overall survival (OS; HR, 1.90; P = 0.002) in the no-thalidomide arm. Conversely, there was a significant clinical benefit of thalidomide for patients with low receptor levels (OS: HR, 0.54; P = 0.015; PFS: HR, 0.54; P = 0.004), mediated most likely by thalidomide's upregulation of NR3C1. In the context of both baseline and relapse parameters, post-relapse survival (PRS) was adversely affected by low NR3C1 levels at relapse in a multivariate analysis (HR, 2.61; P = 0.012). Conclusion: These findings justify the inclusion of NR3C1 expression data in the work-up of patients with myeloma as it can significantly influence the choice of therapy and, ultimately, OS. The identification of an interaction term between thalidomide and NR3C1 underscores the importance of pharmacogenomic studies in the systematic study of new drugs. Clin Cancer Res; 18(19); 5499–506. ©2012 AACR.
Epoetin beta in the treatment of anemia in patients with advanced gastrointestinal cancer.
Authors: B Glimelius, T Linné, K Hoffman, L Larsson, J H Svensson, P Näsman, B Svensson, C Helmers
Journal: Journal of Clinical Oncology (1998)

PURPOSE The possibility that epoetin beta (EPO) could increase hemoglobin (B-Hb) levels and improve quality of life (QoL) in patients with advanced gastrointestinal cancers was investigated. PATIENTS AND METHODS One hundred patients with gastric, pancreatic, biliary, or colorectal cancers and subnormal B-Hb levels were included in a randomized study to test low-dose EPO (2,000 U subcutaneously thrice weekly [2,000 group]) against a higher dose (10,000 U times three [10,000 group]). Eighty-four patients were treated with chemotherapy. QoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 instrument. RESULTS At baseline, mean B-Hb was 108 g/L with no difference between the groups. In the 10,000 group, an increase in B-Hb (&gt;10 g/L) was seen in 30 (73%) patients treated with chemotherapy, after a median of 4 weeks, whereas a corresponding increase in the 2,000 group was seen in 15 (30%) patients after a median of 10 weeks (P &lt; .001). A difference in the proportion of responders (five of eight v one of eight) was also seen in the group of patients not treated with chemotherapy. The proportion of responders was independent of baseline endogenous serum EPO level or observed/predicted log10 serum (S)-EPO levels. Patients who demonstrated improved B-Hb levels also showed improvements in QoL parameters. Tumor response was usually also associated with QoL improvements. CONCLUSION Treatment with EPO at a dose of 10,000 U thrice weekly can rapidly and safely increase B-Hb levels in a high proportion of patients with advanced gastrointestinal cancers. QoL is influenced by the B-Hb increase, but also by the course of the underlying malignancy. It is therefore difficult to define clearly the clinical relevance of the B-Hb increase as such.
Caveolin-1–LRP6 Signaling Module Stimulates Aerobic Glycolysis in Prostate Cancer
Authors: Salahaldin A. Tahir, Guang Yang, Alexei Goltsov, Ki-Duk Song, Chengzhen Ren, Jianxiang Wang, Wenjun Chang, Timothy C. Thompson
Journal: Cancer Research (2013)

Caveolin 1 (Cav-1) is a plasma membrane-associated protein with the capacity to modulate signaling activities in a context-dependent fashion. Interactions between Cav-1 and low-density lipoprotein receptor-related protein 6 (LRP6) were reported to be important for the regulation of Wnt-β-catenin (β-cat) signaling. Cav-1 also interacts with insulin and IGF-I receptors (IGF-IR/IR) and can stimulate IR kinase activities. We found positive correlation between Cav-1 and LRP6 expression in both human primary prostate cancer and metastasis tissues and in PC-3 cells. Cav-1 stimulation of Wnt-β-cat signaling and c-Myc levels was positively associated with LRP6 expression in LNCaP, PC-3, and DU145 prostate cancer cells. Importantly, LRP6 and, to a lesser extent, Cav-1 were found to stimulate aerobic glycolysis. These activities were positively associated with the expression of HK2 and Glut3 and shown to be dependent on Akt signaling by both gene knockdown and chemical inhibition methods. We further showed that Cav-1 and LRP6 exert their effects on Akt and glycolytic activities by stimulating IGF-IR/IR signaling. Overall, our results show that Cav-1 interacts with LRP6 to generate an integrated signaling module that leads to the activation of IGF-IR/IR and results in stimulation of Akt-mTORC1 signaling and aerobic glycolysis in prostate cancer.
Cyclin D1 Activity Regulates Autophagy and Senescence in the Mammary Epithelium
Authors: Nelson E. Brown, Rinath Jeselsohn, Teeru Bihani, Miaofen G. Hu, Parthena Foltopoulou, Charlotte Kuperwasser, Philip W. Hinds
Journal: Cancer Research (2012)

Overexpression of cyclin D1 is believed to endow mammary epithelial cells (MEC) with a proliferative advantage by virtue of its contribution to pRB inactivation. Accordingly, abrogation of the kinase-dependent function of cyclin D1 is sufficient to render mice resistant to breast cancer initiated by ErbB2. Here, we report that mouse cyclin D1(KE/KE) MECs (deficient in cyclin D1 activity) upregulate an autophagy-like process but fail to implement ErbB2-induced senescence in vivo. In addition, immortalized cyclin D1(KE/KE) MECs retain high rates of autophagy and reduced ErbB2-mediated transformation in vitro. However, highlighting its dual role during tumorigenesis, downregulation of autophagy led to an increase in senescence in cyclin D1(KE/KE) MECs. Autophagy upregulation was also confirmed in human mammary epithelial cells (HMEC) subjected to genetic and pharmacologic inhibition of cyclin D1 activity and, similar to our murine system, simultaneous inhibition of Cdk4/6 and autophagy in HMECs enhanced the senescence response. Collectively, our findings suggest a previously unrecognized function of cyclin D1 in suppressing autophagy in the mammary epithelium.
Comparison of ultrasonography, computed tomography and 99mTc liver scan in diagnosis of Budd-Chiari syndrome.
Authors: S Gupta, S Barter, G W Phillips, R N Gibson, H J Hodgson
Journal: Gut (1987)

Ultrasonography, computed tomography and 99mTc liver scanning are all useful in diagnosis of patients with the Budd-Chiari syndrome. In a study to determine their comparative value characteristic findings were recorded in all nine patients at ultrasonography and in seven patients at computed tomography. In contrast 99mTc liver scan showed a characteristic pattern in only one of eight patients. In our experience intrahepatic venous abnormalities were seen better at ultrasonography than at computed tomography. In addition, abnormality in the direction of blood flow could be detected by pulsed Doppler examination. Ultrasonography is relatively inexpensive, readily accessible, does not require administration of radiation or contrast agents and therefore should be the primary non-invasive investigation of patients with Budd-Chiari syndrome, or those at risk of developing it.
Pre- and post-impact muscle activation in the tennis volley: effects of ball speed, ball size and side of the body
Authors: John W Chow, Duane V Knudson, Mark D Tillman, Damon P S Andrew
Journal: British Journal of Sports Medicine (2007)

To examine the pre- and post-impact activation of five upper extremity muscles in the tennis volley across conditions of ball speed, ball type and side of the body.A repeated measures design in a biomechanics laboratory setting was used. A total of 24 recreational tennis players (mean (SD) age 24 (5) years, height 176 (10) cm, mass 76 (13) kg) were recruited from a university. Participants performed tennis volleys under 18 ball conditions: three ball speeds (slow, medium and fast), with three ball types (two oversize and one regular size) each from two sides (forehand and backhand). Average normalised electromyographic levels of the flexor carpi radialis, extensor carpi radialis, triceps brachii, anterior/middle deltoid and posterior/middle deltoid of the hitting arm during pre- and post-impact phases (200 ms before and after ball-racquet impact, respectively) were assessed.For the pre-impact phase, a significant muscle and side interaction (p<0.001) and significant main effects for speed (p = 0.002) and muscle (p<0.001) were observed. For the post-impact phase, significant interactions were observed for ball type and side (p = 0.002), ball speed and side (p = 0.011) and muscle and side (p = 0.001), as well significant main effects for muscle (p<0.001), speed (p = 0.035) and side (p<0.001).Oversize tennis balls do not significantly increase upper extremity muscle activation compared to regular size balls during a tennis volley. The highest post-impact activation was observed in the ECR indicating a vigorous wrist stabilisation role that could irritate players with lateral epicondylalgia.
Orphan lung diseases in childhood: still unadopted?
Authors: A Jaffe
Journal: Thorax (2005)

Despite recent initiatives, the UK is failing adequately to address the inequities in healthcare provision for children with rare lung disease

Money drives research—whether it is for profit by drug companies or for academic status by universities. It is therefore not surprising that little has been done in the past for patients with rare lung diseases, where there is little financial incentive for drug companies or the small population does not merit sufficient grant funding for adequately powered clinical studies. This problem is further compounded in children where research is perceived to be even more difficult. Over the recent years, largely due to extensive lobbying from independent patient support groups, there has been a concerted effort by the European Parliament and the USA government to address these inequities.

The French originally coined the term “orphan” disease, now defined as a disease with a prevalence of less than 5 in 10 000 individuals, and they have been instrumental in addressing the many problems faced by patients suffering from these diseases. It is estimated that there are 7000 rare diseases affecting 27 million people in Europe and a further 27 million in North America. The adoption of recent laws such as the loi sur l’egalite des droits et des chances, la participation et la citoyennete des personnes handicapees (law on equality of rights and opportunities, the participation and the citizenship of the handicapped) by the French Parliament makes specific reference to rare diseases. In addition, European Parliament legislation in 1999 on orphan drug development provides access to treatments for patients with rare diseases and encourages industry to develop new treatments by providing financial inducements. Similar legislation has been in place in the USA since the 1983 Orphan Drug Act. In the USA the Rare Disorders Act of 2002 formally established a statutory …
Elevated circulating CTLA-4 level in patients with COPD is related to systemic inflammation and disease severity
Authors: Liuqun Jia, Yongchun Shen, Hongyu Long, Caishuang Pang, Fuqiang Wen, Tao Wang
Journal: European Respiratory Journal (2013)

Objective : Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) involved in down-regulation of T-cell response, T-cell homeostasis, which plays a role in COPD. The present study aimed to detect the serum level of CTLA-4 in COPD and its relation with systemic inflammation and lung function. Method : 42 COPD patients and 30 controls were recruited, serum was separated immediately and stored at -80° until analysis. Serum CTLA-4 and C-reactive protein (CRP) were analyzed by enzyme-linked immunosorbent assay. Results : The clinical characteristics and levels of CTLA-4, CRP of included subjects were listed in Table 1.

View this table:

Characteristics of included subjects





The mean levels of serum CTLA-4 were significantly elevated in COPD patients when compared to controls (35.29±19.60 vs. 24.94±15.09 pg/ml, p < 0.05). Levels of CRP, were also increased in COPD patients (19.06±5.72 vs. 15.46±5.99 ng/ml, p < 0.05). Regression correlation analysis showed serum CTLA-4 levels were inversely correlated with forced expiratory volume at 1 second (FEV1% predicted) (r=-0.340, p=0.028), while positively correlated with CRP (r=0.434, p=0.004) in COPD group. Conclusion : Serum level of CTLA-4 is higher in COPD patients than controls, and are related with systemic inflammation and disease severity in COPD. These findings suggest circulating CTLA-4 maybe involved in COPD.
Gold Nanorods Conjugated with Doxorubicin and cRGD for Combined Anticancer Drug Delivery and PET Imaging
Authors: Yuling Xiao, Hao Hong, Vyara Z. Matson, Alireza Javadi, Wenjin Xu, Yunan Yang, Yin Zhang, Jonathan W. Engle, Robert J. Nickles, Weibo Cai, Douglas A. Steeber, Shaoqin Gong
Journal: Theranostics (2012)

A multifunctional gold nanorod (GNR)-based nanoplatform for targeted anticancer drug delivery and positron emission tomography (PET) imaging of tumors was developed and characterized. An anti-cancer drug (i.e., doxorubicin (DOX)) was covalently conjugated onto PEGylated (PEG: polyethylene glycol) GNR nanocarriers via a hydrazone bond to achieve pH-sensitive controlled drug release. Tumor-targeting ligands (i.e., the cyclo(Arg-Gly-Asp-D-Phe-Cys) peptides, cRGD) and (64)Cu-chelators (i.e., 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA)) were conjugated onto the distal ends of the PEG arms to achieve active tumor-targeting and PET imaging, respectively. Based on flow cytometry analysis, cRGD-conjugated nanocarriers (i.e., GNR-DOX-cRGD) exhibited a higher cellular uptake and cytotoxicity than non-targeted ones (i.e., GNR-DOX) in vitro. However, GNR-DOX-cRGD and GNR-DOX nanocarriers had similar in vivo biodistribution according to in vivo PET imaging and biodistribution studies. Due to the unique optical properties of GNRs, this multifunctional GNR-based nanoplatform can potentially be optimized for combined cancer therapies (chemotherapy and photothermal therapy) and multimodality imaging (PET, optical, X-ray computed tomography (CT), etc.).
V<scp>ITAMIN</scp>A, I<scp>NFECTION</scp>,<scp>AND</scp>I<scp>MMUNE</scp>F<scp>UNCTION</scp>*
Authors: Charles B Stephensen
Journal: Annual Review of Nutrition (2001)

In populations where vitamin A availability from food is low, infectious diseases can precipitate vitamin A deficiency by decreasing intake, decreasing absorption, and increasing excretion. Infectious diseases that induce the acute-phase response also impair the assessment of vitamin A status by transiently depressing serum retinol concentrations. Vitamin A deficiency impairs innate immunity by impeding normal regeneration of mucosal barriers damaged by infection, and by diminishing the function of neutrophils, macrophages, and natural killer cells. Vitamin A is also required for adaptive immunity and plays a role in the development of T both-helper (Th) cells and B-cells. In particular, vitamin A deficiency diminishes antibody-mediated responses directed by Th2 cells, although some aspects of Th1-mediated immunity are also diminished. These changes in mucosal epithelial regeneration and immune function presumably account for the increased mortality seen in vitamin A-deficient infants, young children, and pregnant women in many areas of the world today.
1158-53 Suppressive effects of eplerenone on accumulation of extra cellular matrix in neointima after coronary stent implantation using swine
Authors: Kohei Wakabayashi, Hiroshi Suzuki, Yoshitaka Iso, Nobuyuki Shimizu, Masayuki Shibata, Yoichi Takeyama
Journal: Journal of the American College of Cardiology (2004)
Cults and zealous self-help movements: a psychiatric perspective
Authors: M Galanter
Journal: American Journal of Psychiatry (1990)

Modern cults and zealous self-help movements exercise an intense group influence and can have a major impact on their members' psychiatric status. On the basis of research findings, the author describes the charismatic group, a generic model for such cohesive, intensely ideological movements. He examines the psychological forces they tap and the way they can both relieve and exacerbate psychopathology. The model is then used to explain the operation of zealous self-help programs that address psychiatric syndromes; these are directed at problems of the medically ill, substance abusers, and relatives of psychiatric patients.