tbuckley/cabot-search huggingface dataset:
Antineutrophil cytoplasmic antibody (ANCA) associated lung-renal vasculitides: A single centre perspective
Authors: Sarah McCloskey, Emma Browne, Matthew Lane, Laura Baines, Alison Brown, James Lordan
Journal: European Respiratory Journal (2012)

Introduction  Small to medium vessel vasculitides are a rare cause of multi-organ failure.  Methods:  This is a single centre retrospective review of systemic vasculitides, with respiratory involvement.  Results:  23 patients (14 Male; 9 Female, mean age 45 (Range 14 to 70) years), presented with vasculitis and significant respiratory involvement, including 17 with ANCA+ vasculitis, 3 ANCA-Neg, and 3 with Churg Strauss Syndrome (CSS). 2 patients had isolated airways disease, 4 systemic non-organ threatening disease, and 14 generalised disease, 7 requiring ventilation and renal replacement.  15 of 20 patients had a biopsy procedure including nasal, skin, bronchial and renal biopsy. 2 patients with ANCA+ vasculitis and 3 with CSS were diagnosed clinically.16 of 20 patients recieved corticosteroids (CS) and cyclophosphamide induction. Maintenance therapy included CS and Azathioprine or Mycophenalate Mofetil. Patients presenting with diffuse alveolar haemorrhage or renal failure received plasma exchange. Rituximab was reserved for patients intolerant or not responding to Cyclophosphamide, or serious relapses, including cerebral vasculitis. Tracheal stenosis (n=1) required recurrent balloon dilatation. Cavitatory pulmonary disease, pneumothorax and aspergillus disease, responded to CS, iv Immunoglobulin and Rituximab.  16 patients relapsed requiring further induction treatment. There were 3 deaths, 1 renal transplant, 1 lung transplant, and 1 end stage renal failure on haemodialysis. The majority of patients are asymptomatic on low dose immunosuppression.  Conclusions:  Pulmonary vasculitis requires a high index of suspicion to ensure prompt diagnosis and treatment to avoid end organ damage.
Prognostic Impact of Specific Chromosomal Aberrations in a Large Group of Pediatric Patients With Acute Myeloid Leukemia Treated Uniformly According to Trial AML-BFM 98
Authors: Christine von Neuhoff, Dirk Reinhardt, Annette Sander, Martin Zimmermann, Jutta Bradtke, David R. Betts, Zuzana Zemanova, Jan Stary, Jean-Pierre Bourquin, Oskar A. Haas, Michael N. Dworzak, Ursula Creutzig
Journal: Journal of Clinical Oncology (2010)

Because cytogenetic data are essential for risk stratification of childhood acute myeloid leukemia (AML), the impact of chromosomal aberrations is crucial.Data of a large group of patients younger than 18 years treated according to study AML-Berlin-Frankfurt-Münster (BFM) 98 (n = 454), including their cytogenetics, were analyzed.The favorable outcome in the subgroups of patients with t(8;21), inv(16), and t(15;17), with an overall survival of 91% (SE, 4%), 92% (SE, 6%), and 87% (SE, 5%), respectively, was confirmed. Within this group, the 5-year probability of event-free survival (pEFS) of all 17 children with t(8;21) and additional aberrations apart from del(9q) or -X/-Y was 100%. As expected, the cytogenetic finding of a complex karyotype (n = 35; pEFS, 33%; SE, 8%) or a monosomy 7 (n = 12; pEFS, 17%; SE, 11%) was associated with a poor outcome. Compared with remaining patients with cytogenetic data (pEFS, 48%; SE, 2%), prognosis in patients with an MLL rearrangement (n = 91) was inferior (pEFS, 34%; SE, 5%; P = .0005). Particularly, children with t(9;11) and additional aberrations (n = 13; pEFS, 31%; SE, 14%) and MLL rearrangements other than t(9;11) and t(11;19) (n = 41; pEFS, 24%; SE, 7%) had an unfavorable outcome. Nine patients with aberrations in 12p showed an adverse prognosis (pEFS, 11%; SE, 10%). The outcome of patients with aberrations of chromosome 5 (n = 13) was better than expected (pEFS, 50%; SE, 13%).Because the prognostic value of rare recurrent chromosomal aberrations still has to be elucidated, these data will contribute to future risk stratification for the treatment of pediatric AML.
BRCA1 Induces Antioxidant Gene Expression and Resistance to Oxidative Stress
Authors: Insoo Bae, Saijun Fan, Qinghui Meng, Jeong Keun Rih, Hee Jong Kim, Hyo Jin Kang, Jingwen Xu, Itzhak D. Goldberg, Anil K. Jaiswal, Eliot M. Rosen
Journal: Cancer Research (2004)

Abstract Mutations of the breast cancer susceptibility gene 1 (BRCA1), a tumor suppressor, confer an increased risk for breast, ovarian, and prostate cancers. To investigate the function of the BRCA1 gene, we performed DNA microarray and confirmatory reverse transcription-PCR analyses to identify BRCA1-regulated gene expression changes. We found that BRCA1 up-regulates the expression of multiple genes involved in the cytoprotective antioxidant response, including glutathione S-transferases, oxidoreductases, and other antioxidant genes. Consistent with these findings, BRCA1 overexpression conferred resistance while BRCA1 deficiency conferred sensitivity to several different oxidizing agents (hydrogen peroxide and paraquat). In addition, in the setting of oxidative stress (due to hydrogen peroxide), BRCA1 shifted the cellular redox balance to a higher ratio of reduced to oxidized glutathione. Finally, BRCA1 stimulated antioxidant response element-driven transcriptional activity and enhanced the activity of the antioxidant response transcription factor nuclear factor erythroid-derived 2 like 2 [also called NRF2 (NFE2L2)]. The ability of BRCA1 to stimulate antioxidant response element-dependent transcription and to protect cells against oxidative stress was attenuated by inhibition of nuclear factor erythroid-derived 2 like 2. These findings suggest a novel function for BRCA1, i.e., to protect cells against oxidative stress. This function would be consistent with the postulated role of BRCA1 as a caretaker gene in preserving genomic integrity.
Key Global Literature
Authors: Vivian Fonseca
Journal: Diabetes Care (2002)

Szabo Z, Arnqvist H, Hakanson E, Jorfeldt L, Svedjeholm R: Effects of high-dose glucose-insulin-potassium on myocardial metabolism after coronary surgery in patients with type II diabetes. Clin Sci 101:37–43, 2001

Findings. Szabo et al. investigated the use of a glucose-insulin-potassium infusion (GIK) on myocardial substrate utilization after coronary surgery in 20 patients with type 2 diabetes. Patients were randomly allocated to either postoperative high-dose GIK or standard postoperative care, including insulin infusion, if necessary, to keep blood glucose <10 mmol/l. Myocardial substrate utilization and hemodynamic status were studied using coronary sinus catheters and Swan-Ganz catheters, respectively. Infusion of GIK caused a shift toward carbohydrate utilization, with significant lactate uptake throughout the study period and significant uptake of glucose after 4 h. Arterial levels of nonesterified fatty acids and β-hydroxybutyric acid decreased, and after 1 h no significant uptake of these substrates was found. Increases in the cardiac index and stroke volume index were found in patients treated with GIK.

Significance. The DIGAMI study clearly established the value of insulin infusions for patients with diabetes presenting with a myocardial infarction. Good diabetic control perioperatively has also been shown to be useful in diabetic subjects undergoing a variety of surgical procedures, including cardiac surgery. The effects of GIK on cardiac metabolism have been studied previously in nondiabetic patients after cardiac surgery. Although patients with diabetes can be expected to benefit most from such treatment, the impact of GIK in diabetic patients undergoing cardiac surgery has not been unexplored. The authors conclude that high-dose GIK can be used in diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of nonesterified fatty acids and β-hydroxybutyric acid.

Clinical Impact. This study adds scientific support to the recommendation of using insulin infusions along with adequate nutrition (glucose) and electrolytes. Perhaps it will help …
Human Monocyte–Derived Dendritic Cells Induce Naive T Cell Differentiation into T Helper Cell Type 2 (Th2) or Th1/Th2 Effectors
Authors: Hiroyuki Tanaka, Christian E. Demeure, Manuel Rubio, Guy Delespesse, Marika Sarfati
Journal: The Journal of Experimental Medicine (2000)

The subset of dendritic cells (DCs) and the nature of the signal inducing DC maturation determine the capacity of DCs to generate polarized immune responses. In this study, we show that the ability of human monocyte-derived DCs (myeloid DC1) to promote T helper type 1 (Th1) or Th2 differentiation was also found to be critically dependent on stimulator/responder ratio. At a low ratio (1:300), mature DCs that have been differentiated after inflammatory (Staphylococcus aureus Cowan 1 or lipopolysaccharide) or T cell–dependent (CD40 ligand) stimulation induced naive T cells to become Th2 (interleukin [IL]-4+, IL-5+, interferon γ) effectors. Th2 differentiation was dependent on B7–CD28 costimulation and enhanced by OX40–OX40 ligand interactions. However, high DC/T cell ratio (1:4) favored a mixed Th1/Th2 cell development. Thus, the fact that the same DC lineage stimulates polarized Th1 or Th2 responses may be relevant since it allows the antigen-presenting cells to initiate an appropriate response for the signal received at the peripheral sites. Controlling the number and the rate of DC migration to the T cell areas in lymphoid tissues may be important for the therapeutic use of DCs.
Prostaglandins and Their Effects on Human Placental Adenyl Cyclase
Authors: Kazuo Satoh, Kenneth J. Ryan
Journal: Journal of Clinical Investigation (1972)

Prostaglandins increased adenyl cyclase activity in human term placental homogenates in a dose-dependent manner during 10-min incubation periods. The potency of the prostaglandins examined was demonstrated to be in the ascending order, prostaglandin F(1alpha) < A(2), F(2alpha), B(2) < A(1) < E(2) < E(1). Although no specific trophic or regulating factors for placental function have been described as yet, it is possible that prostaglandins which are synthesized in decidual tissue could play such a physiological role.
Renal-associated TLR2 mediates ischemia/reperfusion injury in the kidney
Authors: Jaklien C. Leemans, Geurt Stokman, Nike Claessen, Kasper M. Rouschop, Gwendoline J.D. Teske, Carsten J. Kirschning, Shizuo Akira, Tom van der Poll, Jan J. Weening, Sandrine Florquin
Journal: Journal of Clinical Investigation (2005)

TLRs are conserved pattern recognition receptors that detect motifs of pathogens and host material released during injury. For unknown reasons, renal TLR2 mRNA is mainly expressed by tubular cells and is enhanced upon renal ischemia/reperfusion (I/R) injury. We evaluated the role of TLR2 in I/R injury using TLR2-/- and TLR2+/+ mice, TLR2 antisense oligonucleotides, and chimeric mice deficient in leukocyte or renal TLR2. Tubular cells needed TLR2 to produce significant cytokine and chemokine amounts upon ischemia in vitro. TLR2 played a proinflammatory and detrimental role in vivo after I/R injury, as reflected by a reduction in the amount of local cytokines and chemokines, leukocytes, and the level of renal injury and dysfunction in TLR2-/- mice compared with controls. Analysis of chimeric mice suggested that TLR2 expressed on renal parenchyma plays a crucial role in the induction of inflammation and injury. TLR2-antisense treatment protected mice from renal dysfunction, neutrophil influx, and tubular apoptosis after I/R injury compared with nonsense treatment. In summary, we identified renal-associated TLR2 as an important initiator of inflammatory responses leading to renal injury and dysfunction in I/R injury. These data imply that TLR2 blockade could provide a basis for therapeutic strategies to treat or prevent renal ischemic injury.
Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial
Authors: Sean Kehoe, Jane Hook, Matthew Nankivell, Gordon C Jayson, Henry Kitchener, Tito Lopes, David Luesley, Timothy Perren, Selina Bannoo, Monica Mascarenhas, Stephen Dobbs, Sharadah Essapen, Jeremy Twigg, Jonathan Herod, Glenn McCluggage, Mahesh Parmar, Ann-Marie Swart
Journal: The Lancet (2015)
Histologic Demonstration of Antigens Reactive With Anti-p21 &lt;italic&gt;ras&lt;/italic&gt; Monoclonal Antibody (RAP-5) in Human Stomach Cancers&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M Noguchi, S Hirohashi, Y Shimosato, A Thor, J Schlom, Y Tsunokawa, M Terada, T Sugimura
Journal: JNCI Journal of the National Cancer Institute (1986)

The immunohistochemical reactivity of RAP-5, a monoclonal antibody (MoAb) raised against a synthetic peptide corresponding to positions 10-17 of the ras gene product from T24 bladder carcinoma, was studied in 96 surgically resected stomach cancers of humans. The cytoplasm of cancer cells in 65 cases (68%) was positively stained with MoAb RAP-5, although the staining was heterogeneous among cancer cells. There was no definite correlation between depth of tumor invasion and reactivity to MoAb RAP-5. Cancer cells of poorly differentiated tumors showed a tendency to react less frequently and less intensely to MoAb RAP-5. In nontumorous gastric mucosa, parietal cells and some portions of intestinal metaplasia were stained with MoAb RAP-5. These findings suggest an increased expression of the ras gene product (p21) in about two-thirds of gastric adenocarcinomas and in some nonneoplastic gastric epithelial cells.
Toxocara: dogwalking and playing fields
Authors: S Gillespie
Journal: British Journal of Sports Medicine (2001)

In villages, towns, and cities throughout the country, land is set aside for human recreation. Public and private playing fields enable the population to indulge in sport and recreation, but these areas are often convenient for another form of human activity: dog walking. Sportsmen may be concerned that toxocaral infection may be acquired from canine defaecation on public playing fields, and the fastidious groundsmen may remove offending articles before matches are played. However, in doing so, they do little to reduce the risk of toxocaral infection.

Toxocara canis is the round worm (ascarid) parasite of canids: dogs and foxes. It has a complex and unusual life cycle. Eggs, when ingested, hatch in the small intestine and invade the intestinal wall. They are taken up in the portal …
Global Prevalence of Diabetes: Estimates for the Year 2000 and Projections for 2030
Authors: Wolfgang Rathmann, Guido Giani
Journal: Diabetes Care (2004)

Global diabetes prevalence estimates for adults in 2000, which were derived from population-based data using oral glucose tolerance tests, were recently reported by Wild et al. (1). Because there are few OGTT-based data in the European region, estimates from a regional study carried out in the Netherlands were applied to 13 other countries, including Germany (2). For Germany, a prevalence of 4.1% was estimated, which corresponds to 2.6 …
The Mechanisms of Acrylamide Axonopathy
Authors: M S Miller, P S Spencer
Journal: The Annual Review of Pharmacology and Toxicology (1985)

Degeneration of the distal axons of long and large-diameter peripheral nerve fibers is perhaps the most common of all toxic peripheral nerve disorders. Degeneration commonly spreads centrally along affected nerve tracts in a dying-back fashion (1). Axonal disorders of this type are grouped under the term central-peripheral distal axonopathy to emphasize the contemporaneous onset of distal retrograde axonal degeneration in long nerve-fiber tracts in both the central nervous system (CNS) and the peripheral nervous system (PNS) (2). Axonopathy refers exclusively to the primary degeneration of axons, although associated changes may occur in corresponding neuronal perikarya. Schwann cells and oligodendrocytes enveloping affected axons in the PNS and CNS, respectively, commonly undergo secondary changes, induding mitosis and loss of myelin maintenance, while fibroblasts and astrocytes become involved later in the degenerative process. Distal axonopathy can result from a single or, more commonly, repeated exposure to a variety of chemically unrelated agents, or it can occur with apparent spontaneity in a number of abnormal nutritional or metabolic states (3). Although the biochemical mechanisms underlying axonal degeneration are unknown, some progress has been made in recent years in understanding the biochemical events that precede and accompany axon degeneration in certain toxic neuropathies, notably those associated with repeated exposure to acryla­ mide or aliphatic ,),-diketones. Multidisciplinary investigation of these neurop­ athies in laboratory animals and organotypic tissue cultures has revealed several previously unknown basic mechanisms that may be involved in the maintenance of the axon and the initiation and regulation of the degenerative
Elucidating determinants of the plateau in oxygen consumption at o<sub>2</sub>max
Authors: T A Astorino, J Willey, J Kinnahan, S M Larsson, H Welch, L C Dalleck
Journal: British Journal of Sports Medicine (2005)

Background: A plateau in oxygen consumption ( o 2 ) is the primary means of confirming that maximal oxygen uptake ( o 2 max ) is attained during incremental exercise to fatigue. However, it is still unresolved what causes expression of a plateau in o 2 at the end of incremental exercise. Objectives: To elucidate incidence and identify determinants of the o 2 plateau in subjects of varying fitness. Methods: Thirty subjects (mean (SD) age and o 2 max 26.9 (9.8) years and 3.4 (0.8) litre/min respectively) were separated into three groups: endurance trained (ET; n = 9), recreationally active (Rec; n = 11), and strength/sprint trained (STR; n = 10). During three separate visits, subjects completed incremental treadmill exercise during which breath by breath gas exchange data were obtained. Body composition was measured using a three site skinfolds model. Force production of the knee extensors and flexors was assessed using isokinetic dynamometry. Results: o 2 max was significantly higher (p&lt;0.05) in the ET group vs STR and Rec. The change in o 2 (Δ o 2 ) at o 2 max was not different (p&gt;0.05) in the ET group (33.0 (27.3) ml/min) compared with the Rec group (30.3 (24.1) ml/min) and the STR group (44.4 (23.8) ml/min). No correlations (p&gt;0.05) were evident between Δ o 2 at o 2 max and o 2 max ( r = 0.05), fat-free mass ( r = 0.12), and muscular strength ( r = −0.12). Conclusions: The incidence of a plateau in o 2 at o 2 max (from correlation data) is not due to factors related to training status or physical fitness of subjects, but is altered by analysis and interpretation of gas exchange data.
Resolution of Allergic Airway Inflammation and Airway Hyperreactivity Is Mediated by IL-17–producing γδT Cells
Authors: Jenna R. Murdoch, Clare M. Lloyd
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: γδT lymphocytes are enriched within the epithelial microenvironment, where they are thought to maintain homeostasis and limit immunopathology. γδT cells are postulated to exert a regulatory influence during acute allergic airway disease, but the mechanism is unknown. Although regulation of allergic airway disease has been attributed to IL-17–producing T helper (Th) 17 cells, we have found that γδT cells represent the major source of IL-17 in the allergic lung.Objectives: The aim of this study was to determine the contribution of these IL-17–producing γδT cells to regulation of allergic airway inflammation.Methods: Flow cytometry revealed that IL-17–producing γδT cells are more prevalent than IL-17+αβT cells (Th17) in a murine model of ovalbumin-induced allergic inflammation.Measurements and Main Results: Transfer of γδT cells at the peak of acute allergic responses ameliorated airway hyperresponsiveness with a corresponding acceleration in the resolution of eosinophilic and Th2-driven inflammation. Conversely, functional blockade of γδT cells led to exacerbation of injury. Neither treatment changed pulmonary Th17 cell numbers. Moreover, transfer of Th17 cells had no effect on disease outcome. Importantly, IL-17–deficient γδT cells were unable to promote resolution of injury. These data identify IL-17–producing γδT cells as key regulators of the allergic response in vivo.Conclusions: This unfolds a new perspective for the understanding of γδT cell function with regard to innate regulation of the adaptive immune responses, emphasizing that resolution of responses are important in determining the outcome of acute inflammatory episodes as well as for maintenance of tissue integrity and homeostasis.
A Comprehensive DNA Methylation Profile of Epithelial-to-Mesenchymal Transition
Authors: F. Javier Carmona, Veronica Davalos, Enrique Vidal, Antonio Gomez, Holger Heyn, Yutaka Hashimoto, Miguel Vizoso, Anna Martinez-Cardus, Sergi Sayols, Humberto J. Ferreira, Jose V. Sánchez-Mut, Sebastián Morán, Mireia Margelí, Eva Castella, Maria Berdasco, Olafur A. Stefansson, Jorunn E. Eyfjord, Eva Gonzalez-Suarez, Joaquín Dopazo, Modesto Orozco, Ivo G. Gut, Manel Esteller
Journal: Cancer Research (2014)

Epithelial-to-mesenchymal transition (EMT) is a plastic process in which fully differentiated epithelial cells are converted into poorly differentiated, migratory and invasive mesenchymal cells, and it has been related to the metastasis potential of tumors. This is a reversible process and cells can also eventually undergo mesenchymal-to-epithelial transition. The existence of a dynamic EMT process suggests the involvement of epigenetic shifts in the phenotype. Herein, we obtained the DNA methylomes at single-base resolution of Madin-Darby canine kidney cells undergoing EMT and translated the identified differentially methylated regions to human breast cancer cells undergoing a gain of migratory and invasive capabilities associated with the EMT phenotype. We noticed dynamic and reversible changes of DNA methylation, both on promoter sequences and gene-bodies in association with transcription regulation of EMT-related genes. Most importantly, the identified DNA methylation markers of EMT were present in primary mammary tumors in association with the epithelial or the mesenchymal phenotype of the studied breast cancer samples.
GENERAL PRINCIPLES OF PSYCHOTHERAPY
Authors: LEO ALEXANDER
Journal: American Journal of Psychiatry (1950)

I should like to conclude with a few do's and don'ts in the use of psychotherapy in office practice. In general you can't go wrong with a warm, supporting attitude, and in offering the patient opportunity for ventilation. If this ventilation should be associated with a marked emotional abreaction, be sure that you can maintain your objective supporting attitude in the face of this abreaction, even if it should include the expression of hostility toward you. Do not interpret unless you are really sure of your ground—much damage can be done by novices. If the patient improves only at the price of too much dependence on you, or if he should become dependent on you without improving, refer him to a person with more skill and experience in the field of psychiatry. Remember that dependence is regression into an infantile state. While such regression may sometimes be necessary as a transitory phase during treatment, and frequently is undesirable even then, you must ultimately wean your patient and help him to mature. A physician of my acquaintance who rather prides himself on his self-taught skill in his psychotherapeutic management of neurotic patients told me once as a proof of his accomplishments that his cured neurotic patients retained so much confidence in him that for years after treatment they would make no major decision without asking his advice, even in entirely nonmedical matters. To me this sounded as if a surgeon were taking pride in the fact that his patients were letting him dress their still-draining incisions for years after each operation. We must keep our goal firmly in mind, which is to help our patients to achieve health, happiness, maturity, and independence. In every psychotherapy there comes the time when we must throw the ball of responsibility terminedly to our patient, and trust him to carry it.