tbuckley/cabot-search huggingface dataset:
Suppression of Tumor Growth and Metastasis by Simultaneously Blocking Vascular Endothelial Growth Factor (VEGF)–A and VEGF-C with a Receptor-Immunoglobulin Fusion Protein
Authors: Dapeng Zhang, Bohua Li, Jingping Shi, Lei Zhao, Xunming Zhang, Chong Wang, Sheng Hou, Weizhu Qian, Geng Kou, Hao Wang, Yajun Guo
Journal: Cancer Research (2010)

The major cause of cancer mortality is the metastatic spread of tumor cells that can occur via multiple routes, including the vascular system and the lymphatic system. In this study, we developed an IgG-like fusion protein molecule [vascular endothelial growth factor (VEGF) receptor 31-immunoglobulin (VEGFR31-Ig)] which could simultaneously bind the angiogenic growth factor VEGF-A and the lymphangiogenic growth factor VEGF-C. Importantly, VEGFR31-Ig exhibited VEGF-A-binding affinity similar to that of VEGFTrap, the most potent VEGF-A binder, and VEGF-C-binding affinity comparable with that of the soluble fusion protein VEGFR3-Ig (sVEGFR3). Pharmacokinetic analysis in mice showed that VEGFR31-Ig had improved pharmacokinetic properties compared with either VEGFTrap or sVEGFR3. In a highly metastatic human hepatocellular carcinoma (HCCLM3) model in severe combined immunodeficient mice, VEGFR31-Ig potently blocked both tumor angiogenesis and lymphangiogenesis, effectively inhibiting primary tumor growth and metastasis to lungs and lymph nodes. In contrast, VEGFTrap only suppressed primary tumor growth and metastasis to lungs by inhibiting tumor angiogenesis, whereas VEGFR3 was only effective in suppressing tumor metastasis to lymph nodes by blocking tumor lymphangiogenesis. Although a combination of VEGFTrap (25 mg/kg twice weekly) and sVEGFR3 (25 mg/kg twice weekly) can achieve the same therapeutic effect as VEGFR31-Ig (25 mg/kg twice weekly) in the HCCLM3 xenograft mouse model, developing two separate receptor-Ig fusion proteins for clinical use as combination therapy is impractical, mainly owing to regulatory hurdles and cost. Taken together, the VEGFR31-Ig fusion protein presented here has been suggested to have great potential for the treatment of metastatic cancer.
Associations Between Hospital and Surgeon Procedure Volumes and Patient Outcomes After Ovarian Cancer Resection
Authors: Deborah Schrag, Craig Earle, Feng Xu, Katherine S. Panageas, K. Robin Yabroff, Robert E. Bristow, Edward L. Trimble, Joan L. Warren
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Strong associations between provider (i.e., hospital or surgeon) procedure volumes and patient outcomes have been demonstrated for many types of cancer operation. We performed a population-based cohort study to examine these associations for ovarian cancer resections. Methods: We used the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database to identify 2952 patients aged 65 years or older who had surgery for a primary ovarian cancer diagnosed from 1992 through 1999. Hospital- and surgeon-specific procedure volumes were ascertained based on the number of claims submitted during the 8-year study period. Primary outcome measures were mortality at 60 days and 2 years after surgery, and overall survival. Length of hospital stay was also examined. Patient age at diagnosis, race, marital status, comorbid illness, cancer stage, and median income and population density in the area of residence were used to adjust for differences in case mix. All P values are two-sided. Results: Neither hospital- nor surgeon-specific procedure volume was statistically significantly associated with 60-day mortality following primary ovarian cancer resection. However, differences by hospital volume were seen with 2-year mortality; patients treated at the low-, intermediate-, and high-volume hospitals had 2-year mortality rates of 45.2% (95% confidence interval [CI] = 42.1% to 48.4%), 41.1% (95% CI = 38.1% to 44.3%), and 40.4% (95% CI = 37.4% to 43.4%), respectively. The inverse association between hospital procedure volume and 2-year mortality was statistically significant both before ( P = .011) and after ( P = .006) case-mix adjustment but not after adjustment for surgeon volume. Two-year mortality for patients treated by low-, intermediate-, and high-volume surgeons was 43.2% (95% CI = 40.7% to 45.8%), 42.9% (95% CI = 39.5% to 46.4%), and 39.5% (95% CI = 36.0% to 43.2%), respectively; there was no association between 2-year mortality and surgeon procedure volume, with or without case-mix adjustment. After case-mix adjustment, neither hospital volume ( P = .031) nor surgeon volume ( P = .062) was strongly associated with overall survival. Conclusion: Hospital- and surgeon-specific procedure volumes are not strong predictors of survival outcomes following surgery for ovarian cancer among women aged 65 years or older.
Ly-49 mediates EL4 lymphoma adhesion to isolated class I major histocompatibility complex molecules.
Authors: K P Kane
Journal: The Journal of Experimental Medicine (1994)

Ly-49 is a recently identified cell surface molecule expressed on a subpopulation of natural killer (NK) cells and certain T lymphomas. It has been suggested, based on gene transfection and antibody blocking studies, that Ly-49 is a negative regulator of NK lytic activity, possibly through an interaction with target cell class I molecules. However, it has not been demonstrated that class I molecules indeed serve as ligands for Ly-49. We have found that T lymphomas expressing Ly-49 bind isolated class I major histocompatibility complex (MHC) molecules but not class II molecules immobilized on plastic. Adhesion to class I molecules was not found with T lymphomas lacking Ly-49 expression. The Ly-49 expressing EL4 lymphoma bound Dd, Dk, and Kb, but not Kd, Kk, or Db, thus demonstrating a restricted pattern of class I adhesion. The observed cell adhesion was class I density dependent, and binding to Dd and Dk was extensively inhibited by the A1 monoclonal antibody directed against Ly-49. These results provide direct evidence for Ly-49 serving as a receptor for a subset of class I MHC molecules.
Platelets pull in progenitors
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

![][1] 

Bone marrow–derived progenitor cells (BM-PC) bind directly to platelets (Plt) at sites of blood vessel injury.

Clot-forming platelets lure vessel-rebuilding progenitor cells to sites of blood vessel injury, according to Massberg and colleagues on page [1221][2].

Injured
Negative pressure ventilation versus conventional mechanical ventilation in the treatment of acute respiratory failure in COPD patients
Authors: A Corrado, M Gorini, R Ginanni, C Pelagatti, G Villella, U Buoncristiano, F Guidi, E Pagni, A Peris, E De Paola
Journal: European Respiratory Journal (1998)

This case-control study was aimed to evaluate the effectiveness of negative pressure ventilation (NPV) versus conventional mechanical ventilation (CMV) for the treatment of acute respiratory failure (ARF) in patients with chronic obstructive pulmonary disease (COPD) admitted to a respiratory intermediate intensive care unit (RIICU) and four general intensive care units (ICU). Twenty-six COPD patients in ARF admitted in 1994-95 to RIICU and treated with NPV (cases) were matched according to age (+/-5 yrs), sex, causes triggering ARF, Acute Physiology and Chronic Health Evaluation (APACHE) II score (+/- 5 points), pH (+/-0.05) and arterial carbon dioxide tension (Pa,CO2) on admission with 26 patients admitted to ICU and treated with CMV (controls). The primary end points of the study were inhospital death for both groups and the need for endotracheal intubation for cases. The secondary endpoints were length and complications of mechanical ventilation and length of hospital stay. The effectiveness of matching was 91%. Mortality rate was 23% for cases and 27% for controls (NS), five cases needed endotracheal intubation, four of whom subsequently died. The duration of ventilation in survivors was significantly lower in cases than in controls, with a median of 16 h (range 2-111) versus 96 h (range 12-336) (P&lt;0.02), whereas the length of hospital stay was similar in the two groups, with a median of 12 days (range 2-47) for cases vs 12 days (range 3-43) (NS) for controls. No complications were observed in cases, whereas three controls developed infective complications. These results suggest that negative pressure ventilation is as efficacious as conventional mechanical ventilation for the treatment of acute respiratory failure in patients with chronic obstructive pulmonary disease and that it is associated with a shorter duration of ventilation and a similar length of hospital stay compared with conventional mechanical ventilation.
Virus-specific T lymphocytes home to the skin during natural dengue infection
Authors: Laura Rivino, Emmanuelle A. Kumaran, Tun-Linn Thein, Chien Tei Too, Victor Chih Hao Gan, Brendon J. Hanson, Annelies Wilder-Smith, Antonio Bertoletti, Nicholas R. J. Gascoigne, David Chien Lye, Yee Sin Leo, Arne N. Akbar, David M. Kemeny, Paul A. MacAry
Journal: Science Translational Medicine (2015)

Circulating virus-specific T lymphocytes may contribute to immune surveillance against dengue in the skin.
Heterotachy Processes in Rhodophyte-Derived Secondhand Plastid Genes: Implications for Addressing the Origin and Evolution of Dinoflagellate Plastids
Authors: Kamran Shalchian-Tabrizi, Marianne Skånseng, Fredrik Ronquist, Dag Klaveness, Tsvetan R. Bachvaroff, Charles F. Delwiche, Andreas Botnen, Torstein Tengs, Kjetill S. Jakobsen
Journal: Molecular Biology and Evolution (2006)

Serial transfer of plastids from one eukaryotic host to another is the key process involved in evolution of secondhand plastids. Such transfers drastically change the environment of the plastids and hence the selection regimes, presumably leading to changes over time in the characteristics of plastid gene evolution and to misleading phylogenetic inferences. About half of the dinoflagellate protists species are photosynthetic and unique in harboring a diversity of plastids acquired from a wide range of eukaryotic algae. They are therefore ideal for studying evolutionary processes of plastids gained through secondary and tertiary endosymbioses. In the light of these processes, we have evaluated the origin of 2 types of dinoflagellate plastids, containing the peridinin or 19′-hexanoyloxyfucoxanthin (19′-HNOF) pigments, by inferring the phylogeny using "covarion" evolutionary models allowing the pattern of among-site rate variation to change over time. Our investigations of genes from secondary and tertiary plastids derived from the rhodophyte plastid lineage clearly reveal "heterotachy" processes characterized as stationary covarion substitution patterns and changes in proportion of variable sites across sequences. Failure to accommodate covarion-like substitution patterns can have strong effects on the plastid tree topology. Importantly, multigene analyses performed with probabilistic methods using among-site rate and covarion models of evolution conflict with proposed single origin of the peridinin- and 19′-HNOF–containing plastids, suggesting that analysis of secondhand plastids can be hampered by convergence in the evolutionary signature of the plastid DNA sequences. Another type of sequence convergence was detected at protein level involving the psaA gene. Excluding the psaA sequence from a concatenated protein alignment grouped the peridinin plastid with haptophytes, congruent with all DNA trees. Altogether, taking account of complex processes involved in the evolution of dinoflagellate plastid sequences (both at the DNA and amino acid level), we demonstrate the difficulty of excluding independent, tertiary origin for both the peridinin and 19′-HNOF plastids involving engulfment of haptophyte-like algae. In addition, the refined topologies suggest the red algal order, Porphyridales, as the endosymbiont ancestor of the secondary plastids in cryptophytes, haptophytes, and heterokonts.
Serious adverse events during a 6-min walk test in patients with pulmonary hypertension
Authors: Norman R. Morris, Helen Seale, Julie Harris, Kathleen Hall, Peter Hopkins, Fiona Kermeen
Journal: European Respiratory Journal (2015)

The 6-min walk test (6MWT) is well standardised and, as per current guidelines, is deemed safe to perform in a range of patients [1]. In pulmonary arterial hypertension (PAH), 6-min walk distance (6MWD) is an important predictor of mortality and morbidity [2]. Moreover, changes in the 6MWD have been the primary end-point of most pivotal randomised controlled trials that have assessed the clinical response to specific pharmacological therapies in PAH [2]. The first ever reported cases of serious adverse events during the 6MWT in patients with pulmonary hypertension <http://ow.ly/FdVp8> The authors would like to thank Associate Professor Anne Holland (La Trobe University, Melbourne, Australia) for her comments on this manuscript.
Bullous Eruption Associated With Heroin Pulmonary Edema
Authors: Seymour Katz
Journal: JAMA (1971)

<h3>To the Editor.—</h3> In support of the report of traumatic skin lesions in drug-induced coma, by Mandy and Ackerman (<b>213:</b>253-256, 1970), we offer the following observations made in November 1968 at the Bronx Municipal Hospital Center. <h3>Report of a Case.—</h3> A 26-year-old man was found unconscious at home and brought to the hospital. Other than "flu-like" symptoms during the preceding week, he was reported to have been in excellent health and was not known to be a user of heroin. Physical examination revealed a well-nourished, comatose man with a temperature of 106.8 F. blood pressure of 100/70 mm Hg, heart rate of 120 beats per minute, and respiratory rate of 26 per minute. His skin was hot and erythematous; there were circinate erythematous streaks on the insteps of both feet and an urticarial eruption on the right palm and right ear. The pupils were miotic, there were bilateral basilar
A functional ryanodine-sensitive intracellular Ca2+ store is present in vascular endothelial cells.
Authors: R C Ziegelstein, H A Spurgeon, R Pili, A Passaniti, L Cheng, S Corda, E G Lakatta, M C Capogrossi
Journal: Circulation Research (1994)

The presence of the ryanodine receptor was recently demonstrated in vascular and endocardial endothelium, but its function has not been established. We investigated whether functional ryanodine-sensitive Ca2+ stores are present in cultured endothelial cells from rat aorta (RAECs), human aorta (HAECs), human umbilical vein (HUVECs), and bovine pulmonary artery (BPAECs) and what role these may play in intracellular Ca2+ regulation. Under resting conditions, HAECs, BPAECs, and HUVECs demonstrated a slow increase in intracellular Ca2+ (indexed by indo 1 fluorescence) on exposure to 5 mumol/L ryanodine, whereas RAECs did not. However, after an initial bradykinin exposure in RAECs, ryanodine markedly blunted the rapid increase in Ca2+ on a second exposure to bradykinin. In HUVECs, ryanodine in buffer with 1.5 mmol/L Ca2+ did not inhibit the agonist-sensitive Ca2+ increase, whereas it blunted the rapid increase in Ca2+ on histamine exposure in buffer with 5 mmol/L Ca2+, suggesting that increasing [Ca2+] enhances the binding of ryanodine to its receptor. Thus, functional ryanodine-sensitive Ca2+ stores are present in vascular endothelial cells. These appear to be involved in regulation of Ca2+ storage and release from agonist-sensitive intracellular compartments.
Randomized, Placebo-Controlled Trial of Platelet Glycoprotein IIb/IIIa Blockade With Primary Angioplasty for Acute Myocardial Infarction
Authors: Sorin J. Brener, Lawrence A. Barr, J. E. B. Burchenal, Stanley Katz, Barry S. George, Ancil A. Jones, Eric D. Cohen, Phillip C. Gainey, Harvey J. White, H. Barrett Cheek, Jeffrey W. Moses, David J. Moliterno, Mark B. Effron, Eric J. Topol
Journal: Circulation (1998)

Background —The benefit of catheter-based reperfusion for acute myocardial infarction (MI) is limited by a 5% to 15% incidence of in-hospital major ischemic events, usually caused by infarct artery reocclusion, and a 20% to 40% need for repeat percutaneous or surgical revascularization. Platelets play a key role in the process of early infarct artery reocclusion, but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospectively evaluated in the setting of acute MI. Methods and Results —Patients with acute MI of &lt;12 hours’ duration were randomized, on a double-blind basis, to placebo or abciximab if they were deemed candidates for primary PTCA. The primary efficacy end point was death, reinfarction, or any (urgent or elective) target vessel revascularization (TVR) at 6 months by intention-to-treat (ITT) analysis. Other key prespecified end points were early (7 and 30 days) death, reinfarction, or urgent TVR. The baseline clinical and angiographic variables of the 483 (242 placebo and 241 abciximab) patients were balanced. There was no difference in the incidence of the primary 6-month end point (ITT analysis) in the 2 groups (28.1% and 28.2%, P =0.97, of the placebo and abciximab patients, respectively). However, abciximab significantly reduced the incidence of death, reinfarction, or urgent TVR at all time points assessed (9.9% versus 3.3%, P =0.003, at 7 days; 11.2% versus 5.8%, P =0.03, at 30 days; and 17.8% versus 11.6%, P =0.05, at 6 months). Analysis by actual treatment with PTCA and study drug demonstrated a considerable effect of abciximab with respect to death or reinfarction: 4.7% versus 1.4%, P =0.047, at 7 days; 5.8% versus 3.2%, P =0.20, at 30 days; and 12.0% versus 6.9%, P =0.07, at 6 months. The need for unplanned, “bail-out” stenting was reduced by 42% in the abciximab group (20.4% versus 11.9%, P =0.008). Major bleeding occurred significantly more frequently in the abciximab group (16.6% versus 9.5%, P =0.02), mostly at the arterial access site. There was no intracranial hemorrhage in either group. Conclusions —Aggressive platelet inhibition with abciximab during primary PTCA for acute MI yielded a substantial reduction in the acute (30-day) phase for death, reinfarction, and urgent target vessel revascularization. However, the bleeding rates were excessive, and the 6-month primary end point, which included elective revascularization, was not favorably affected.
Elizabeth Timgwilian Davies-Humphreys Christopher Adrian Holborow Frederick James Gordon ("Jimmy") Jefferiss Philip Vincent Kielty Harvey McTaggart Susan Lynn Maxwell Francis John Milward Dushyanthan ("Dushy") Surendranath Nadarajah Jeremiah Gerard Dermot O'Sullivan Douglas Wyness Thomson ("Doug") Paul Brian Stephen Quinn Irwin Bruce Speight Felix Ernest Weale
Authors: J. Davies-Humphreys, R. Zeegen, J R W Harris, V. Kielty, H. Jones, G. McNaught, A. Brown, S Montgomery, P Le Feuvre, T. Milward, A Santhakumaran, G J O'Sullivan, I. Burns, N. Quinn, E L. Speight, N. Rothnie
Journal: BMJ (1998)

Westminster 1930), d
Development of heart block in SSA/SSB autoantibody-positive pregnancies is associated with maternal age and display a season-of-birth pattern
Authors: A. Ambrosi, S. Salomonsson, H. Eliasson, E. Zeffer, V. Dzikaite, G. Bergman, E. Fernlund, E. Theander, A. Rydberg, T. Skogh, S. Wallberg-Jonsson, A. Ohman, U. Lundstrom, M. Mellander, O. Winqvist, M. Fored, A. Ekbom, L. Alfredsson, H. Kallberg, F. Gadler, A. Jonzon, S.-E. Sonesson, M. Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Congenital heart block (CHB) may develop in the fetus of anti-Ro/SSA and anti-La/SSB positive mothers. Reported recurrence rates of only 10–20% despite persisting maternal antibodies indicate that additional factors are critical for establishment of the heart block. The authors therefore investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. <h3>Material and methods</h3> The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families including Ro/La-positive (n= 190) and Ro/La-negative (n=165) pregnancies. <h3>Results</h3> The authors observed a recurrence rate for heart block of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was however significantly higher than in pregnancies resulting in babies without heart block (p&lt;0.01). Seasonal timing of pregnancy appeared to be an important factor in pregnancy outcome in Ro/La-positive women as the ratio of affected to healthy births in the summer (June–August) was significantly different from the rest of the year, corresponding to a higher proportion of children with heart block born in the summer compared to the rest of the year. This in turn corresponds to a higher proportion of affected pregnancies for which the susceptible gestational weeks 18–24 occur during the late winter (January–March). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. <h3>Conclusions</h3> This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for CHB development in Ro/La positive pregnancy. These observations will be important for counselling when a pregnancy is considered.
Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in mice
Authors: Scott C. Kogan, Jerrold M. Ward, Miriam R. Anver, Jules J. Berman, Cory Brayton, Robert D. Cardiff, John S. Carter, Sherri de Coronado, James R. Downing, Torgny N. Fredrickson, Diana C. Haines, Alan W. Harris, Nancy Lee Harris, Hiroshi Hiai, Elaine S. Jaffe, Ian C. M. MacLennan, Pier Paolo Pandolfi, Paul K. Pattengale, Archibald S. Perkins, R. Mark Simpson, Mark S. Tuttle, Joanne F. Wong, Herbert C. Morse
Journal: Blood (2002)
Unmyelinated tactile afferents signal touch and project to insular cortex
Authors: H. Olausson, Y. Lamarre, H. Backlund, C. Morin, B.G. Wallin, G. Starck, S. Ekholm, I. Strigo, K. Worsley, Å.B. Vallbo, M.C. Bushnell
Journal: Nature Neuroscience (2002)