tbuckley/cabot-search huggingface dataset:
THE CATALYTIC ACTIVITY OF THE DEVELOPING HEN'S EGG
Authors: M. C. Winternitz, W. B. Rogers
Journal: The Journal of Experimental Medicine (1910)

A. The catalytic activity of the tissues of newly born and adult rabbits. 1. There is practically no difference between the catalytic power of the blood, brain or muscle of newly born and adult rabbits. 2. The kidneys and lungs are less active in the newly born, but increase rapidly during the first days of life. 3. The liver is more active in the newly born than in the adult rabbit. B. The catalytic activity of the developing hen's egg. 1. The entire fresh egg has a slight but definite catalytic power which remains practically constant even though the egg be kept for several months at room temperature. 2. The separate parts of the egg, germinal center, yolk and white have practically no activity when tested individually. 3. The entire unfertilized egg shows no catalytic activity even after incubation at 38 degrees C. for twenty-one days. 4. The germinal portion of the incubated fertilized egg rapidly acquires the power of decomposing hydrogen peroxide, while the yolk and white together or separately show no such increase, nor is there any activity to be found in the amniotic fluid. 5. It seems, therefore, that the catalytic power of the developing egg is formed from the contents of the egg which themselves show little action, by the developing germinal portion, independent of all external influences except heat (38 degrees C.) and air.
Gas compression artefacts when testing peak expiratory flow meters with mechanically-driven syringes
Authors: D Navajas, J Roca, R Farre, M Rotger
Journal: European Respiratory Journal (1997)

Mechanically-driven syringes used to test peak expiratory flow (PEF) meters must produce the American Thoracic Society (ATS) standard waveforms with PEF accuracy of 2%. However, gas compression within the syringe could result in significant PEF inaccuracy when testing high resistance meters. The gas compression artefact was investigated in a mechanical syringe (PWG; MH Custom Design &amp; Mfg L.C., Midvale, Ut, USA) of 13.6 L connected to a standard range mini-Wright PEF meter (Clement Clarke International, Harlow, UK). Scaled versions of the ATS standard waveform No. 24, with peak flows of 750 and 450 L x min(-1), were discharged through the PEF meter from different starting piston positions to vary syringe volume (Vsyr). The PEF recorded by the meter decreased linearly with increasing Vsyr. PEF decreased by 0.31 and 0.27% per litre for the ATS standard waveforms with PEF of 750 and 450 L x min(-1), respectively. The target PEF computed from piston displacement overread the actual PEF delivered into the PEF meter by approximately 4% when Vsyr = 13.6 L. Overreading fell to approximately 1% when Vsyr was reduced to 3.62 L. Therefore, gas compression error in commercially available large mechanical syringes can exceed the 2% inaccuracy limit when testing high resistance portable PEF meters. Measurements can be corrected for gas compression by linearly extrapolating PEF recordings to zero volume.
Return to play and physical performance tests: evidence-based, rough guess or charade?
Authors: Eric J Hegedus, Chad E Cook
Journal: British Journal of Sports Medicine (2015)

It was with great interest that we read the recent BMJ editorial by professors Lohmander and Roos1 that challenged the orthopaedic and sports world to have greater evidence to support interventions. We would place ourselves firmly on their bandwagon as we examine the evidence supporting physical performance tests (PPTs) in athletes.

A PPT is aptly named as each requires an athlete to perform a physical task that is believed to be a component of sports activity. PPTs are simple, portable, low-tech assessments and as such, are quite attractive. Representative of PPTs is the single leg hop test2 and its variations (triple, crossover, and timed 6 m hop), which are ubiquitous in sports rehabilitation environments. PPTs are routinely used to predict/determine if: 

1.  An athlete will be injured at some future time based on substandard performance of the test (injury prediction);

2.  The athlete will perform at a higher level than his or her peers for the foreseeable future …
Phase I Clinical and Pharmacokinetic Study of Oral Sapacitabine in Patients With Acute Leukemia and Myelodysplastic Syndrome
Authors: Hagop Kantarjian, Guillermo Garcia-Manero, Susan O'Brien, Stefan Faderl, Farhad Ravandi, Robert Westwood, Simon R. Green, Judy H. Chiao, Patricia A. Boone, Jorge Cortes, William Plunkett
Journal: Journal of Clinical Oncology (2009)

Sapacitabine is an oral deoxycytidine nucleoside analog with a unique mechanism of action that is different from cytarabine.To define the dose-limiting toxicities (DLT) and maximum-tolerated dose (MTD) of sapacitabine given orally twice daily for 7 days every 3 to 4 weeks, or twice daily for 3 days for 2 weeks (days 1 through 3 and days 8 through 10) every 3 to 4 weeks, in refractory-relapse acute leukemia and myelodysplastic syndrome (MDS). A total of 47 patients were treated in the phase I study that used a classical 3 + 3 design. Sapacitabine was escalated from 75 to 375 mg twice daily for 7 days (n = 35) and from 375 to 475 mg twice daily for 3 days on days 1 through 3 and days 8 through 10.The DLTs with both schedules were gastrointestinal. The MTDs were 375 mg twice daily for 7 days and 425 mg twice daily for 3 days on days 1 through 3 and days 8 through 10. The recommended phase II single-agent dose schedules were 325 mg twice daily for 7 days and 425 mg twice daily for 3 days on days 1 through 3 and days 8 through 10. Responses were observed in 13 patients (28%); four were complete responses, and nine were marrow complete responses.Sapacitabine is a new, safely administered, oral deoxycytidine analog that has encouraging activity in leukemia and MDS. Phase II studies are ongoing.
Cross-presentation of glycolipid from tumor cells loaded with α-galactosylceramide leads to potent and long-lived T cell–mediated immunity via dendritic cells
Authors: Kanako Shimizu, Yuri Kurosawa, Masaru Taniguchi, Ralph M. Steinman, Shin-ichiro Fujii
Journal: The Journal of Experimental Medicine (2007)

We report a mechanism to induce combined and long-lived CD4+ and CD8+ T cell immunity to several mouse tumors. Surprisingly, the initial source of antigen is a single low dose of tumor cells loaded with α-galactosylceramide (α-GalCer) glycolipid (tumor/Gal) but lacking co-stimulatory molecules. After tumor/Gal injection intravenously (i.v.), innate NKT and NK cells reject the tumor cells, some of which are taken up by dendritic cells (DCs). The DCs in turn cross-present glycolipid on CD1d molecules to NKT cells and undergo maturation. For B16 melanoma cells loaded with α-GalCer (B16/Gal), interferon γ–producing CD8+ T cells develop toward several melanoma peptides, again after a single low i.v. dose of B16/Gal. In all four poorly immunogenic tumors tested, a single dose of tumor/Gal i.v. allows mice to become resistant to tumors given subcutaneously. Resistance requires CD4+ and CD8+ cells, as well as DCs, and persists for 6–12 mo. Therefore, several immunogenic features of DCs are engaged by the CD1d-mediated cross-presentation of glycolipid-loaded tumor cells, leading to particularly strong and long-lived adaptive immunity.
Smallpox in Staffordshire, 1947
Authors: C. S. Smith
Journal: BMJ (1948)

Much has been accomplished, and the start is a promising one.*At other universities plans are being developed which will contribute to the same end.Differing in detail and shaped by local conditions, they will provide a welcome stimulus through rivalry.There is still a long way to go before the aim of the University of London is realized and before the peculiar opportunities present here in London are developed fully.When that time comes the postgraduate institutes will send out the future leaders of medical thought and practice, and will be able to welcome those who seek to advance knowledge by research and to improve their skill for the relief of suffering.
Bone Sialoprotein, Matrix Metalloproteinase 2, and v 3 Integrin in Osteotropic Cancer Cell Invasion
Authors: A. Karadag, K. U. E. Ogbureke, N. S. Fedarko, L. W. Fisher
Journal: JNCI Journal of the National Cancer Institute (2004)

Bone sialoprotein (BSP) interacts separately with both matrix metalloproteinase 2 (MMP-2) and integrin alpha(v)beta3 and is overexpressed in many metastatic tumors. Its role in tumor biology, however, remains unclear. We investigated whether BSP enhances cancer cell invasiveness by forming a trimolecular complex with MMP-2 and cell-surface integrin alpha(v)beta3.Invasiveness of breast, prostate, lung, and thyroid tumor cell lines was measured with a modified Boyden chamber assay. Binding and co-localization of BSP, MMP-2, and integrin alpha(v)beta3 were investigated with immunoprecipitation and in situ hybridization. All statistical tests were two-sided.Treatment with BSP increased invasiveness of many breast, prostate, lung, and thyroid cancer cells through Matrigel in a dose-dependent manner. BSP at 50 nM increased the invasiveness of SW-579 thyroid cancer cells (95.2 units, 95% confidence interval [CI] = 90.4 to 100 units) by approximately 10-fold compared with that of untreated control SW-579 cells (9.1 units, 95% CI = 5.7 to 12.5 units) (P<.001). Addition of an inactive mutated BSP, in which BSP's integrin-binding RGD tripeptide was altered, or addition of integrin alpha(v)beta3-blocking antibodies resulted in invasiveness equivalent to that of untreated cells. Inhibiting cellular MMP-2 activity with chemical inhibitors or a specific antibody also blocked BSP-enhanced invasiveness. Osteopontin and dentin matrix protein 1, proteins related to BSP that also bind integrin alpha(v)beta3 and form complexes with other MMPs (but not MMP-2), did not enhance invasiveness. Immunoprecipitation showed that a complex containing BSP, integrin alpha(v)beta3, and MMP-2 formed in vitro. Addition of BSP increased the amount of MMP-2 bound by cells in an integrin-dependent fashion. Co-expression of BSP, integrin alpha(v)beta3, and MMP-2 in papillary thyroid carcinoma cells was shown by in situ hybridization.Cancer cells appear to become more invasive when BSP forms a cell-surface trimolecular complex by linking MMP-2 to integrin alpha(v)beta3.
Vandetanib for the Treatment of Medullary Thyroid Cancer
Authors: Nicole G. Chau, Robert I. Haddad
Journal: Clinical Cancer Research (2012)

Vandetanib (ZD6474, Caprelsa, AstraZeneca), an oral small-molecule tyrosine kinase inhibitor (TKI) that targets the rearranged during transfection receptor (RET), VEGF receptor (VEGFR2-3), and EGF receptor (EGFR), is the first systemic therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of symptomatic or progressive advanced medullary thyroid cancer (MTC). In a randomized phase III trial of patients with unresectable, locally advanced, or metastatic MTC, vandetanib improved progression-free survival compared with placebo [HR, 0.46; 95% confidence interval (CI), 0.31-0.69; P < 0.001]. However, the benefits in delaying disease progression need to be balanced against the associated and potentially serious toxicities, including diarrhea, hypertension, and QTc prolongation. Here, we review the clinical development of vandetanib leading to its integration into the current treatment paradigm and highlight the ongoing and future challenges in TKI use in MTC.
Efficacy and Safety Analysis of Epoetin Alfa in Patients With Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Thomas Grote, Allen L. Yeilding, Rene Castillo, Dean Butler, Ellioth Fishkin, David H. Henry, Michael DeLeo, Kenneth Fink, Daniel J. Sullivan
Journal: Journal of Clinical Oncology (2005)

This randomized, double-blind, placebo-controlled trial (N93-004) evaluated the effects of epoetin alfa on tumor response to chemotherapy and survival in patients with small-cell lung cancer (SCLC).Adult patients with hemoglobin < or = 14.5 g/dL starting chemotherapy received epoetin alfa 150 U/kg or placebo subcutaneously 3 times weekly until 3 weeks after completion of chemotherapy. Survival was assessed for 3 years. The primary end point was the proportion of patients with complete or partial response after three chemotherapy cycles.The trial was terminated prematurely after 224 of a projected 400 patients were accrued. Baseline characteristics were similar between groups. Epoetin alfa and placebo patients (n = 109 and n = 115, respectively) had mean baseline hemoglobin of 12.8 g/dL and 13.0 g/dL, respectively. Overall tumor response was similar between the epoetin alfa and placebo groups after three chemotherapy cycles (72% and 67%, respectively; 95% CI of difference, -6% to 18%) and after completion of chemotherapy (60% and 56%, respectively; 95% CI of difference, -9% to 17%). Epoetin alfa and placebo groups had similar median overall survival (10.5 and 10.4 months, respectively) and overall mortality (91.7% and 87.8%, respectively; hazard ratio, 1.172; 95% CI, 0.887 to 1.549; P = .264). Hemoglobin was maintained in the prechemotherapy range in epoetin alfa patients, but decreased substantially in placebo patients. Fewer epoetin alfa patients than placebo patients required transfusion.These results suggest that in newly diagnosed patients with SCLC epoetin alfa does not affect tumor response to chemotherapy or survival. However, the early trial closure makes these conclusions preliminary.
Multiple phenotypically distinct smooth muscle cell populations exist in the adult and developing bovine pulmonary arterial media in vivo.
Authors: M G Frid, E P Moiseeva, K R Stenmark
Journal: Circulation Research (1994)

Different smooth muscle cell (SMC) functions may require different cell phenotypes. Because the main pulmonary artery performs diverse functions, we hypothesized that it would contain heterogeneous SMC populations. If the hypothesis were confirmed, we wished to determine the developmental origin of the different populations. Using specific antibodies, we analyzed the expression of smooth muscle (SM) contractile and cytoskeletal proteins (alpha-SM-actin, SM myosin, calponin, desmin, and meta-vinculin) in the main pulmonary artery of fetal (60 to 270 days of gestation), neonatal, and adult animals. We demonstrated the existence of a complex, site-specific heterogeneity in the structure and cellular composition of the pulmonary arterial wall. We found that at least four cell/SMC phenotypes, based on immunobiochemical characteristics, cell morphology, and elastic lamellae arrangement pattern, were simultaneously expressed within the mature arterial media. Further, we were able to assess phenotypic alterations in each of the four identified cell populations during development. We found that each cell population within the arterial media expressed alpha-SM-actin at least at certain stages of development, thus demonstrating its smooth muscle identity. However, each cell population progressed along different developmental pathways, suggesting the existence of multiple and distinct cell lineages. A novel anti-metavinculin antibody described in this study reliably distinguished one SMC population from the others during all the developmental stages analyzed. We conclude that the pulmonary arterial media is indeed composed of multiple phenotypically distinct cell/SMC populations with unique lineages. We speculate that these distinct cell populations may serve different functions within the arterial media and may also respond in unique ways to pathophysiological stimuli.
Pilot scheme will ask GPs to give more detail in sickness certificates
Authors: Adrian O’Dowd
Journal: BMJ (2008)

Doctors could be asked to advise employers on what kind of work can be done by staff members who are off sick, the government has announced.

The health secretary, Alan Johnson, is keen to change what he has called the United Kingdom’s “sick note culture” into a “well note culture,” but doctors’ leaders say that it should not be for GPs to police people over their capability to work.

Carol Black, the government’s national director for health and work, will soon publish her review of the health of the working age population.

In the meantime Mr Johnson has previewed some of the proposals, including testing …
Health related quality of life in patients with rhinitis is low compared with the healthy population
Authors: Howraman Meteran, Simon Francis Thomsen, Vibeke Backer
Journal: European Respiratory Journal (2013)

Aim: To compare health related quality of life in rhinitis patients with the normal population, and to

identify predictors of health related quality of life in rhinitis patients.

Methods: A total of 696 patients with rhinitis, 14-44 years of age, were interviewed about upper and lower respiratory symptoms, and skin test reactivity, lung function, and airway responsiveness were measured. The SF-36 scoring instrument assessed health related quality of life according to eight domains. Mental and physical component summaries (MCS and PCS) were computed.

Results: SF-36 scores among rhinitis patients were lower than in the reference population for all domains, particularly MCS. Low MCS among rhinitis patients were predicted by: male sex (p=0.001), smoking (p=0,029), eczema (p=0.007), food allergy (p=0.007) and nasal stenosis (p=0.006), whereas low PCS was predicted by: male sex (p=0.006), asthma (p=0.001), recurring sinusitis (p=0.001), airway hyperresponsiveness (p=0.001) and nasal stenosis (p=0.003). There was as linear decrease in MCS (p=0.001) and PCS (p=0.001) according to increasing severity of asthma (measured by GINA score) among rhinitis patients.

Conclusion: Patients with rhinitis have a poor health related quality of life compared with the healthy general population. Male sex, smoking, asthma (severity), nasal stenosis, eczema, food allergy and airway hyperresponsiveness determine health related quality of life in rhinitis patients.
Mechanism of Gram-positive Shock: Identification of Peptidoglycan and Lipoteichoic Acid Moieties Essential in the Induction of Nitric Oxide Synthase, Shock, and Multiple Organ Failure
Authors: Ken M. Kengatharan, Sjef De Kimpe, Caroline Robson, Simon J. Foster, Christoph Thiemermann
Journal: The Journal of Experimental Medicine (1998)

The incidence of septic shock caused by gram-positive bacteria has risen markedly in the last few years. It is largely unclear how gram-positive bacteria (which do not contain endotoxin) cause shock and multiple organ failure. We have discovered recently that two cell wall fragments of the pathogenic gram-positive bacterium Staphylococcus aureus, lipoteichoic acid (LTA) and peptidoglycan (PepG), synergize to cause the induction of nitric oxide (NO) formation, shock, and organ injury in the rat. We report here that a specific fragment of PepG, N-acetylglucosamine-β-[1→ 4]-N-acetylmuramyl-l-alanine–d-isoglutamine, is the moiety within the PepG polymer responsible for the synergism with LTA (or the cytokine interferon γ) to induce NO formation in the murine macrophage cell line J774.2. However, this moiety is also present in the PepG of the nonpathogenic bacterium Bacillus subtilis. We have discovered subsequently that S. aureus LTA synergizes with PepG from either bacterium to cause enhanced NO formation, shock, and organ injury in the rat, whereas the LTA from B. subtilis does not synergize with PepG of either bacterium. Thus, we propose that the structure of LTA determines the ability of a particular bacterium to cause shock and multiple organ failure (pathogenicity), while PepG acts to amplify any response induced by LTA.
Synergistic Effect of Histone Deacetylase Inhibitors FK228 and m-Carboxycinnamic Acid Bis-Hydroxamide with Proteasome Inhibitors PSI and PS-341 against Gastrointestinal Adenocarcinoma Cells
Authors: Masaaki Adachi, YuBin Zhang, Xudong Zhao, Takae Minami, Rina Kawamura, Yuji Hinoda, Kohzoh Imai
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We investigated whether the histone deacetylase inhibitors m-carboxycinnamic acid bis-hydroxamide (CBHA) and a bicyclic depsipeptide, FK228, can enhance the anticancer effect of the proteasome inhibitors PSI and PS-341 in gastrointestinal carcinoma cells. Experimental Design: The anticancer effect of CBHA or FK228 and PSI or PS-341 was evaluated by cell death, caspase-3 activity, externalization of phosphatidylserine and DNA fragmentation, and colony formation assay. Expression of apoptosis-related molecules and cell cycle regulatory molecules, as well as phosphorylation of p38 were investigated by immunoblots. Generation of reactive oxygen species (ROS) was detected by intracellular oxidation of 5- (and-6)-carboxy-2′,7′-dichlorodihydrofluorescein diacetate. Results: CBHA or FK228 plus PSI or PS-341 synergistically induced apoptosis in human colonic DLD-1 and gastric MKN45 carcinoma cell lines. CBHA or FK228, but not 5-fluorouracil, plus PS-341 strongly decreased plating efficiency of DLD-1 cells. FK228 elicited ROS generation, and the free radical scavenger l-N-acetylcysteine inhibited the synergistic anticancer effect of combined therapy. In addition, l-N-acetylcysteine inhibited the combined therapy-mediated elevation of a proapoptotic BH3-only protein Bim expression, phosphorylation of H2AX, and accumulation of 8-hydroxydeoxyguanosine. Conclusions: FK228 or CBHA and PSI or PS-341 synergistically induce apoptosis in DLD-1 and MKN45 cells depending on ROS-mediated signals. Our data suggest that a combination of FK228 or CBHA with PSI or PS-341 may be a valuable therapy against gastrointestinal adenocarcinoma cells.
Magnetic resonance cholangiopancreatography
Authors: PHILIP W BEARCROFT, DAVID J LOMAS
Journal: Gut (1997)

Magnetic resonance cholangiopancreatographyNon-invasive imaging techniques such as ultrasound (US) or computed tomography (CT) are widely used for the diagnosis and monitoring of many pancreatic and biliary tract diseases.However, these techniques have limitations, such as the low sensitivity of ultrasound for detecting common duct calculi, which means that the diagnosis of several common conditions including tumours (benign and malignant), calculi, sclerosing cholangitis and chronic pancreatitis may still require invasive procedures such as endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC).These invasive techniques also have disadvantages-for example, ERCP requires direct cannulation of the common bile or pancreatic duct, sedation, the use of ionising radiation and a team of trained, experienced personnel.Complications include haemorrhage, sepsis, pancreatitis, bile leakage, as well as a recognised mortality. 1ERCP may not be technically possible and this, along with the complication rate, has been related to operator experience. 2 In clinical practice these complications are usually oVset by the diagnostic information obtained and the ability to proceed immediately to therapeutic intervention when required.Magnetic resonance cholangiopancreatography (MRCP) is a relatively new technique for non-invasive imaging of the biliary and pancreatic duct systems.Early trials suggest that it may have a useful role in clinical practice.