tbuckley/cabot-search huggingface dataset:
One visual system with two interacting visual streams
Authors: Jason S. McCarley, Gregory J. DiGirolamo
Journal: Behavioral and Brain Sciences (2002)

Norman's aim to reconcile two longstanding and seemingly opposed philosophies of perception, the constructivist and the ecological, by casting them as approaches to complementary subsystems within the visual brain is laudable. Unfortunately, Norman overreaches in attempting to equate direct perception with dorsal/unconscious visual processing and indirect perception with ventral/conscious visual processing. Even a cursory review suggests that the functional and neural segregation of direct and indirect perception is not as clear as the target article would suggest.
Phase II Trial of Bevacizumab and Everolimus in Patients With Advanced Renal Cell Carcinoma
Authors: John D. Hainsworth, David R. Spigel, Howard A. Burris, David Waterhouse, Bobby L. Clark, Robert Whorf
Journal: Journal of Clinical Oncology (2010)

Purpose To evaluate the efficacy and toxicity of the combination of bevacizumab, an angiogenesis inhibitor, and everolimus, an mTOR inhibitor, in the treatment of patients with advanced clear cell renal carcinoma. Patients and Methods Two groups of patients with metastatic renal cell carcinoma were eligible for this study: those with no previous treatment with targeted agents and those with previous treatment with sunitinib and/or sorafenib. All patients received bevacizumab 10 mg/kg intravenously every 2 weeks and everolimus 10 mg orally daily. Patients were evaluated for response after 8 weeks of treatment; patients with objective response or stable disease continued treatment until disease progression or unacceptable toxicity occurred. Results Eighty patients (50 untreated, 30 previously treated) entered this clinical trial. The combination of bevacizumab/everolimus showed activity in both groups. Median progression-free survivals in previously untreated and previously treated patients were 9.1 and 7.1 months, respectively. Overall response rates (30% and 23%) were similar in both groups. The regimen was well tolerated by most patients, with a toxicity profile as expected based on the known toxicities of these two agents. Grade 3 to 4 proteinuria was more frequent than expected (25%) and led to treatment discontinuation in six patients. Conclusion Bevacizumab/everolimus is active and well tolerated in the treatment of advanced clear cell renal cancer, either as first-line treatment or after treatment with sunitinib and/or sorafenib. The benefits of this combination regimen, versus sequential use of these two agents, requires further study.
Current Approaches to Diagnosis and Treatment of Invasive Aspergillosis
Authors: Brahm H. Segal, Thomas J. Walsh
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Filamentous fungi (moulds) are ubiquitous soil inhabitants whose conidia are inhaled into the respiratory tract, where they may cause life-threatening infections. Among these infections is invasive aspergillosis, which is a major cause of morbidity and mortality in the severely immunocompromised. Risk factors for invasive aspergillosis include prolonged and severe neutropenia, hematopoietic stem cell and solid organ transplantation, advanced AIDS, and chronic granulomatous disease. Invasive aspergillosis most commonly involves the sinopulmonary tract reflecting inhalation as the principal portal of entry. Chest computed tomography scans and new non-culture-based assays such as antigen detection and polymerase chain reaction may facilitate the early diagnosis of invasive aspergillosis, but have limitations. Reflecting an important unmet need, there has been a significant expansion in the antifungal armamentarium. The second-generation triazole, voriconazole, was superior to conventional amphotericin B as primary therapy for invasive aspergillosis, and is the new standard of care for this infection. There is significant interest in combination antifungal therapy pairing an echinocandin with either an azole or amphotericin B formulation as therapy for invasive aspergillosis. In addition, there has been an increased understanding of the immunology of Aspergillus infection, paving the way to novel immune augmentation strategies in animal models that merit evaluation in phase I clinic trials.
Short term effect of intermittent negative pressure ventilation in COPD patients with respiratory failure
Authors: N Ambrosino, T Montagna, S Nava, A Negri, S Brega, C Fracchia, L Zocchi, C Rampulla
Journal: European Respiratory Journal (1990)

Ten patients with stable chronic obstructive pulmonary disease (COPD) and hypercapnic respiratory failure were randomly submitted to intermittent negative pressure ventilation (INPV) 6 h per day for 5 consecutive days by either a cuirass or pneumo wrap ventilator. The effects were assessed by measurements of spirometry, blood gases, maximal inspiratory (MIP) and expiratory (MEP) pressures, 12 minutes walking distance test (12 mwd), sensation of dyspnoea by a visual analogue scale (VAS) and diaphragmatic electromyographic activity (Edi). Edi was recorded during INPV sessions in only 7 patients. The same measurements apart from Edi were also performed in 8 matched control patients randomly submitted to conventional physiotherapy. During INPV, Edi activity was reduced, at least temporarily down to 50% of baseline values. Comparison of baseline with post INPV values showed no changes in thoracic gas volume (TGV), forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC), arterial oxygen partial pressure (Pao2) and MEP; significant improvements were seen in MIP, vital capacity (VC), VAS, and 12 mwd only in patients submitted to INPV. A significant improvement in PaCO2 was observed in both groups of patients. We conclude that INPV may be effective in improving the functional reserve of the inspiratory muscles in selected COPD patients with hypercapnic respiratory failure and signs of inspiratory muscle dysfunction.
Alcoholic cirrhosis is a good indication for liver transplantation, even for cases of recidivism
Authors: G-P Pageaux, J Michel, V Coste, P Perney, P Possoz, P-F Perrigault, F Navarro, J-M Fabre, J Domergue, P Blanc, D Larrey
Journal: Gut (1999)

BACKGROUND/AIMS Alcoholic cirrhosis remains a controversial indication for liver transplantation, mainly because of ethical considerations related to the shortage of donor livers. The aim of this study was to review experience to date, focusing on survival rates and complications, and the effect of alcohol relapse on outcome and alterations in marital and socioprofessional status. METHODS The results for 53 patients transplanted for alcoholic cirrhosis between 1989 and 1994 were compared with those for 48 patients transplanted for non-alcoholic liver disease. The following variables were analysed: survival, rejection, infection, cancer, retransplantation, employment and marital status, alcoholic recurrence. The same variables were compared between alcohol relapsers and non-relapsers. RESULTS Recovery of employment was the only significantly different variable between alcoholic (30%) and non-alcoholic patients (60%). Two factors influenced survival in the absence of alcohol recidivism: age and abstinence before transplantation. For all other variables, there were no differences between alcoholic and non-alcoholic patients, and, within the alcoholic group, between relapsers and non-relapsers. The recidivism rate was 32%. CONCLUSION The data indicate that liver transplantation is justified for alcoholic cirrhosis, even in cases of recidivism, which did no affect survival and compliance with the immunosuppressive regimen. These good results should help in educating the general population about alcoholic disease.
Arsenic trioxide in comparison with chemotherapy and bone marrow transplantation for the treatment of relapsed acute promyelocytic leukaemia
Authors: W.Y. Au, A.K.W. Lie, C.S. Chim, R. Liang, S.K. Ma, C.H. Chan, Y.K. Mak, Y.T. Chen, C.C. So, Y.M. Yeung, S.F. Yip, L.G. Wong, J.C. Chan, S.Y. Liu, Y.L. Kwong
Journal: Annals of Oncology (2003)
Extracapsular Extension of Pelvic Lymph Node Metastases From Urothelial Carcinoma of the Bladder Is an Independent Prognostic Factor
Authors: Achim Fleischmann, George N. Thalmann, Regula Markwalder, Urs E. Studer
Journal: Journal of Clinical Oncology (2005)

To analyze the prognostic impact of risk factors for urothelial carcinoma of the bladder (UCB) with pelvic lymph node (LN) metastases.We analyzed a consecutive series of 507 patients with UCB who were preoperatively staged N0M0. One hundred one of 124 eligible patients who were treated with radical cystectomy and standardized extended bilateral pelvic lymphadenectomy with curative intent and had postoperatively confirmed LN metastases were evaluated in regard to recurrence-free and overall survival.A median of 22 nodes per patient (range, 10 to 43 nodes) were removed and examined. Median recurrence-free and overall survival durations were 17 months and 21 months (range for both, 1 to 191 months), respectively. In the multivariate analysis for recurrence-free survival, extracapsular extension of LN metastases was the strongest prognostic factor (P = .019). Other variables such as tumor stage (pT1/2 v pT3 and pT4), the number (< five v >/= five), and the percentage (< 20% v >/= 20%) of metastatic nodes had a significant influence on recurrence-free and overall survival in the univariate analysis. However, they all failed to be significant prognostic factors in the multivariate analysis.The results of this study indicate that radical cystectomy with bilateral lymphadenectomy can have a curative effect in a subset of patients with pelvic LN positive UCB. Provided that a representative number of LNs are removed by meticulous lymphadenectomy and that a thorough histologic examination is performed, prognosis for such patients can be determined quite reliably. In the multivariate analysis, extracapsular extension of LN metastases was the strongest factor predicting prognosis.
Gestational diabetes mellitus
Authors: Thomas A. Buchanan, Anny H. Xiang
Journal: Journal of Clinical Investigation (2005)

Gestational diabetes mellitus (GDM) is defined as glucose intolerance of various degrees that is first detected during pregnancy. GDM is detected through the screening of pregnant women for clinical risk factors and, among at-risk women, testing for abnormal glucose tolerance that is usually, but not invariably, mild and asymptomatic. GDM appears to result from the same broad spectrum of physiological and genetic abnormalities that characterize diabetes outside of pregnancy. Indeed, women with GDM are at high risk for having or developing diabetes when they are not pregnant. Thus, GDM provides a unique opportunity to study the early pathogenesis of diabetes and to develop interventions to prevent the disease.
Interleukin 6 production in experimental cerebral malaria: modulation by anticytokine antibodies and possible role in hypergammaglobulinemia.
Authors: G E Grau, K Frei, P F Piguet, A Fontana, H Heremans, A Billiau, P Vassalli, P H Lambert
Journal: The Journal of Experimental Medicine (1990)

The production of Interleukin 6 (IL-6) was studied during experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. IL-6 is present in the serum of mice with ECM, the highest concentrations being observed in mice with full-blown neurological syndrome. High IL-6 levels were also observed, however, in the absence of pathology in nonlethal malaria infection. These data suggest that IL-6 is produced in large amounts during malaria infection, but does not play a major role in the pathogenesis of ECM. A modulation of IL-6 production in ECM was achieved by in vivo treatment with other anticytokine antibodies: antibodies to interferon (IFN-gamma) or to tumor necrosis factor (TNF) abolished the rise of IL-6, while anti-IL-3 and anti-granulocyte/macrophage colony-stimulating factor antibodies only partially prevented this rise, suggesting that the two cytokines IFN-gamma and TNF are important intermediates in IL-6 production. Passive immunization against IL-6 did not prevent ECM, but significantly reduced serum IgG levels in malaria-infected mice. Thus, by its effects on B cells, IL-6 may be involved in hypergammaglobulinemia and immune-complex diseases, e.g., glomerulonephritis observed during malaria infection.
Excitation–Transcription Coupling in Arterial Smooth Muscle
Authors: Brian R. Wamhoff, Douglas K. Bowles, Gary K. Owens
Journal: Circulation Research (2006)

The primary function of the vascular smooth muscle cell (SMC) is contraction for which SMCs express a selective repertoire of genes (eg, SM alpha-actin, SM myosin heavy chain [SMMHC], myocardin) that ultimately define the SMC from other muscle cell types. Moreover, the SMC exhibits extensive phenotypic diversity and plasticity, which play an important role during normal development, repair of vascular injury, and in vascular disease states. Diverse signals modulate ion channel activity in the sarcolemma of SMCs, resulting in altered intracellular calcium (Ca) signaling, activation of multiple intracellular signaling cascades, and SMC contraction or relaxation, a process known as "excitation-contraction coupling" (EC-coupling). Over the past 5 years, exciting new studies have shown that the same signals that regulate EC-coupling in SMCs are also capable of regulating SMC-selective gene expression programs, a new paradigm coined "excitation-transcription coupling" (ET-coupling). This article reviews recent progress in our understanding of the mechanisms by which ET-coupling selectively coordinates the expression of distinct gene subsets in SMCs by disparate transcription factors, including CREB, NFAT, and myocardin, via selective kinases. For example, L-type voltage-gated Ca2+ channels modulate SMC differentiation marker gene expression, eg, SM alpha-actin and SMMHC, via Rho kinase and myocardin and also regulate c-fos gene expression independently via CaMK. In addition, we discuss the potential role of IK channels and TRPC in ET-coupling as potential mediators of SMC phenotypic modulation, ie, negatively regulate SMC differentiation marker genes, in vascular disease.
Impaired Angiogenesis in the Remnant Kidney Model
Authors: DUK-HEE KANG, JEREMY HUGHES, MARILDA MAZZALI, GEORGE F. SCHREINER, RICHARD J. JOHNSON
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Impaired angiogenesis and decreased vascular endothelial growth factor (VEGF) expression were recently documented in the remnant kidney (RK) model of progressive renal failure. VEGF (50 μg/kg, twice daily) was administered to RK rats between weeks 4 and 8 after surgery, and rats were euthanized at week 8 for histologic study. During the administration of VEGF ( n = 7) or vehicle ( n = 6), systemic BP was comparable in the two groups. VEGF treatment resulted in improved renal function and lower mortality rates, compared with the vehicle-treated group. Renal histologic analyses confirmed a 3.5-fold increase in glomerular endothelial cell proliferation (0.14 ± 0.03 versus 0.04 ± 0.02 proliferating endothelial cells/glomerulus, VEGF versus vehicle, P &lt; 0.05), a twofold increase in peritubular capillary endothelial cell proliferation (1.60 ± 0.30 versus 0.78 ± 0.17 cells/mm 2 , VEGF versus vehicle, P &lt; 0.01), a threefold decrease in peritubular capillary rarefaction ( P &lt; 0.01), and a twofold increase in endothelial nitrix oxide synthase expression ( P &lt; 0.05) in the VEGF-treated group; an eightfold increase in urinary nitrate/nitrite levels ( P &lt; 0.05) was also noted. Although the difference in glomerulosclerosis scores did not reach statistical significance (0.67 ± 0.42 versus 1.22 ± 0.63, VEGF versus vehicle; range, 0 to 4; P = NS), VEGF-treated rats exhibited less interstitial collagen type III deposition (9.32 ± 3.26 versus 17.45 ± 7.50%, VEGF versus vehicle, P &lt; 0.01) and reduced tubular epithelial cell injury, as manifested by osteopontin expression (5.57 ± 1.60 versus 9.58 ± 3.45%, VEGF versus vehicle, P &lt; 0.01). In conclusion, VEGF treatment reduces fibrosis and stabilizes renal function in the RK model. The use of angiogenic factors may represent a new approach to the treatment of kidney disease.
THE CYTOTOXIC EFFECT OF MOUSE MACROPHAGES ON SYNGENEIC AND ALLOGENEIC ERYTHROCYTES
Authors: H. Melsom, R. Seljelid
Journal: The Journal of Experimental Medicine (1973)

A cytotoxic effect of mouse peritoneal macrophages against syngeneic and allogeneic erythrocytes was demonstrated by isotope release and release of hemoglobin. The cytotoxic effect was dependent on the contact between viable, activated macrophages and target cells. Activation was accomplished by prolonged cultivation of macrophages and by the presence of Zn++ and Con-A. Immunization did not prove necessary. Morphological observations as well as experiments with various salt concentrations indicate that the cytotoxic reaction may involve some kind of osmotic effect upon the target cells.
Level of knowledge and information sources used by patients with psoriasis
Authors: S.W. LANIGAN, ALISON LAYTON
Journal: British Journal of Dermatology (1991)

One-hundred and eight patients with psoriasis completed a questionnaire concerning their knowledge about the condition. This was carried out at two departments of dermatology, at Bridgend General Hospital and Leeds General Infirmary. There were no significant differences between the two centres, and the main source of the patients' information about psoriasis was from a dermatologist, but several other sources such as newsletter were of help.
<i>Mycobacterium tuberculosis pks12</i> Produces a Novel Polyketide Presented by CD1c to T Cells
Authors: Isamu Matsunaga, Apoorva Bhatt, David C. Young, Tan-Yun Cheng, Stephen J. Eyles, Gurdyal S. Besra, Volker Briken, Steven A. Porcelli, Catherine E. Costello, William R. Jacobs, D. Branch Moody
Journal: The Journal of Experimental Medicine (2004)

CD1c-mediated T cells are activated by a mycobacterial phospholipid antigen whose carbohydrate structure precisely corresponds to mammalian mannosyl β-1-phosphodolichol (MPD), but contains an unusual lipid moiety. Here, we show that this T cell antigen is a member of a family of branched, alkane lipids that vary in length (C30-34) and are produced by medically important mycobacteria such as M. tuberculosis and M. bovis Bacille-Calmette-Guerin. The alkane moiety distinguished these mycobacterial lipid antigens from mammalian MPDs and was necessary for activation of CD1c-restricted T cells, but could not be accounted for by any known lipid biosynthetic pathway. Metabolic labeling and mass spectrometric analyses suggested a mechanism for elongating lipids using alternating C2 and C3 units, rather than C5 isopentenyl pyrophosphate. Inspection of the M. tuberculosis genome identified one candidate gene, pks12, which was predicted to encode the largest protein in M. tuberculosis, consisting of 12 catalytic domains that correspond to key steps in the proposed pathway. Genetic deletion and complementation showed that Pks12 was necessary for antigen production, but did not affect synthesis of true isoprenols. These studies establish the genetic and enzymatic basis for a previously unknown type of polyketide, designated mycoketide, which contains a lipidic pathogen-associated molecular pattern.
CXC Chemokines IP-10 and Mig Expression and Direct Migration of Pulmonary CD8 + /CXCR3 + T Cells in the Lungs of Patients with HIV Infection and T-Cell Alveolitis
Authors: CARLO AGOSTINI, MONICA FACCO, MARTA SIVIERO, DAVIDE CAROLLO, SILVIA GALVAN, ANNA MARIA CATTELAN, RENATO ZAMBELLO, LIVIO TRENTIN, GIANPIETRO SEMENZATO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The recruitment of cytotoxic T lymphocytes (CTL) is considered to be the major tool for the clearance of HIV from the lower respiratory tract. In this study we evaluated the pathophysiologic role of two lymphotactic CXC chemokines (IP-10 and Mig) in the lung of HIV-infected patients. These chemokines stimulate the directional migration of activated T cells and interact with a specific receptor (CXC receptor 3, CXCR3). Lymphocytes recovered from the bronchoalveolar lavage (BAL) of HIV-infected patients with high intensity T-cell alveolitis were CD8 + T cells expressing high levels of CXCR3 and IFN- γ , a phenotype that is characteristic of Tc1 cells. Pulmonary T cells expressing CXCR3 exhibited a high migratory capability in response to IP-10 and Mig. Alveolar macrophages recovered from patients with T-cell alveolitis bore the IFN- γ -inducible proteins IP-10 and Mig. A positive correlation was demonstrated between IP-10, Mig, and IL-15 expression by alveolar macrophages. Interestingly, macrophages isolated from the lung of HIV-infected patients with T-cell alveolitis secreted definite levels of CXCR3 ligands capable of inducing T-cell chemotaxis. Taken together, our data suggest that chemotactic ligands that bind CXCR3 contribute significantly to the accumulation of HIV-specific CTL in the lung.
Red meat and cancer risk in a network of case–control studies focusing on cooking practices
Authors: M. Di Maso, R. Talamini, C. Bosetti, M. Montella, A. Zucchetto, M. Libra, E. Negri, F. Levi, C. La Vecchia, S. Franceschi, D. Serraino, J. Polesel
Journal: Annals of Oncology (2013)
Topische Diagnose der Gehirnkrankheiten, eine klinische Studie
Authors: Von Herman Nothnagel
Journal: American Journal of Psychiatry (1881)

declared was not seclusion, "they only reported seclusion when the shutter of the window was closed * This sounds strange when we remember the Lancet'8 violent denunciations of the "hideous torture"by the shower bath in American Asylums.
Physicians' and patients' choices in evidence based practice
Authors: R B. Haynes
Journal: BMJ (2002)

Voltage-gated sodium channels are the primary target of pyrethroid insecticides. Although it is well known that specific mutations in insect sodium channels confer knockdown resistance (kdr) to pyrethroids, the atomic mechanisms of pyrethroid-sodium channel interactions are not clearly understood. Previously, computer modeling and mutational analysis predicted two pyrethroid receptors, pyrethroid receptor site 1 (PyR1) (initial) and pyrethroid receptor site 2 (PyR2), located in the domain interfaces II/III and I/II, respectively. The models differ in ligand orientation and the number of transmembrane helices involved. In this study, we elaborated a revised PyR1 model of the mosquito sodium channel. Computational docking in the K<sub>v</sub>1.2-based open channel model yielded a complex in which a pyrethroid (deltamethrin) binds between the linker helix IIL45 and transmembrane helices IIS5, IIS6, and IIIS6 with its dibromoethenyl and diphenylether moieties oriented in the intra- and extracellular directions, respectively. The PyR2 and revised PyR1 models explained recently discovered kdr mutations and predicted new deltamethrin-channel contacts. Further model-driven mutagenesis identified seven new pyrethroid-sensing residues, three in the revised PyR1 and four in PyR2. Our data support the following conclusions: 1) each pyrethroid receptor is formed by a linker-helix L45 and three transmembrane helices (S5 and two S6s); 2) IIS6 contains four residues that contribute to PyR1 and another four to PyR2; 3) seven pairs of pyrethroid-sensing residues are located in symmetric positions within PyR1 and PyR2; and 4) pyrethroids bind to PyR1 and PyR2 in similar orientations, penetrating deeply into the respective domain interfaces. Our study elaborates the dual pyrethroid-receptor sites concept and provides a structural background for rational development of new insecticides.
The wallstent in native coronary arteries (WIN), multicenter trial: acute results and 6 months follow-up of the feasibility Cohort
Authors: L. Bilodeau, T. Schreiber, J.D. Hilton, S. Rosenblum, S. Mehta, M. McIvor, Z. Krajcer, B.H. Wilson, C. Senerchia, L.D. Beck, A. Pedan
Journal: Journal of the American College of Cardiology (1998)