tbuckley/cabot-search huggingface dataset:
Streptococcal M6 protein expressed in Escherichia coli. Localization, purification, and comparison with streptococcal-derived M protein.
Authors: V A Fischetti, K F Jones, B N Manjula, J R Scott
Journal: The Journal of Experimental Medicine (1984)

Type 6 streptococcal M protein produced by E. coli bearing plasmid pJRS42.13 (ColiM6) accumulates in the periplasmic space of this new host. No immunoreactive M protein was found either on the surface of the organism or in the culture medium. The ColiM6 protein was purified from the periplasm and the final preparation consisted of three protein bands of apparent molecular weight 55,000, 57,000, and 59,000. These three bands were identical in migration in SDS PAGE to that of the M protein present in freshly prepared crude periplasm. The amino acid composition of the ColiM6 protein was nearly identical to that of M protein isolated from streptococci with phage lysin (LysM6). Furthermore, except for the amino terminal residue of the LysM6 molecule, the amino terminal sequence of the ColiM6 molecule was identical to those of both LysM6 and M protein released from the streptococcus by limited peptic digestion (PepM6). These results reveal that the molecule produced in the E. coli and transported into the periplasm may be the complete M protein as it exists on the streptococcus. The results also indicate that the systems that process M protein for transport through the cytoplasmic membrane are similar in the streptococcus and E. coli. The purified ColiM6 protein was able to remove opsonic antibodies from both human and rabbit serum, as well as to stimulate the production of opsonic antibodies in rabbits, indicating that the immunodeterminants on this molecule are the same as those found on streptococcal-derived M molecules.
Anoxia-hyperoxia induces monocyte-derived interleukin-8.
Authors: A P Metinko, S L Kunkel, T J Standiford, R M Strieter
Journal: Journal of Clinical Investigation (1992)

Ischemia-reperfusion and hyperoxia-induced pulmonary injury are associated with the presence of activated neutrophils (PMN) and cellular injury. Although the signals orchestrating the directed migration of these PMN during the pathogenesis of these disease states remain to be fully elucidated, it appears they may be dependent upon the production of certain neutrophil activating/chemotactic factors such as C5a, leukotriene B4, platelet-activating factor, and IL-8. The production of the latter chemotaxin by mononuclear phagocytes is especially intriguing as these cells can mediate inflammatory cell migration by either directly generating IL-8, or by inducing its production from surrounding nonimmune cells. In light of these observations, we propose that ischemia-reperfusion and oxidant stress, in vivo, may be simulated by anoxia-hyperoxia induced stress in vitro, and that this stress may act as a stimulus for the production of IL-8. We now show that isolated human blood monocytes respond to such an oxygen stress with augmented production of IL-8. In initial studies, monocytes demonstrated an increase in the production of IL-8 under anoxic preconditioning. Subsequently, monocytes were cultured under one of the following conditions for 24 h: (a) room air/5% CO2; (b) 95% N2/5% CO2 for 6 h, followed by room air/5% CO2 for 18 h; (c) 95% N2/5% CO2 for 6 h, followed by 95% O2/5% CO2 for 18 h; (d) room air/5% CO2 for 6 h, followed by 95% O2/5% CO2 for 18 h; or (e) 95% O2/5% CO2. Supernatants were isolated and analyzed for IL-8 antigen by specific IL-8 ELISA, demonstrating the production of monocyte-derived IL-8: 5.9 +/- 0.9, 11.4 +/- 1.7, 21.1 +/- 2.3, 14.6 +/- 2.4, and 26.3 +/- 4.7, ng/ml by designated conditions a, b, c, d, and e listed above, respectively. This variance in IL-8 production reflects altered rates of transcription as shown by Northern blot analysis and nuclear run-off assay. Furthermore, when monocytes were concomitantly treated with LPS (100 ng/ml) under in vitro hyperoxic conditions, both IL-8 steady-state mRNA and antigenic activity were two- to threefold greater than under room air conditions. The association of anoxic preconditioning and oxygen stress with augmented production of monocyte-derived IL-8 support the potential role for ischemia-reperfusion and hyperoxia-induced IL-8 production in vivo, providing a possible mechanism for PMN migration/activation in disease states characterized by altered tissue oxygenation.
A Rose Is No Longer a Rose
Authors: I. Craig Henderson
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.06.617 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12177095 A Rose Is No Longer a Rose I. Craig HendersonxI. Craig HendersonSearch for articles by this author Show More University of California, San Francisco, San Francisco, CA https://doi.org/10.1200/JCO.2002.06.617 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Latitude, Birth Date, and Allergy
Authors: Matthias Wjst, Shyamali Dharmage, Elisabeth André, Dan Norback, Chantal Raherison, Simona Villani, Jure Manfreda, Jordi Sunyer, Deborah Jarvis, Peter Burney, Cecilie Svanes
Journal: PLoS Medicine (2005)

Background The space and time distribution of risk factors for allergic diseases may provide insights into disease mechanisms. Allergy is believed to vary by month of birth, but multinational studies taking into account latitude have not been conducted. Methods and Findings A questionnaire was distributed in 54 centres to a representative sample of 20- to 44-y-old men and women mainly in Europe but also including regions in North Africa, India, North America, Australia, and New Zealand. Data from 200,682 participants were analyzed. The median prevalence of allergic rhinitis was 22%, with a substantial variation across centres. Overall, allergic rhinitis decreased with geographical latitude, but there were many exceptions. No increase in prevalence during certain winters could be observed. Also, no altered risk by birth month was found, except borderline reduced risks in September and October. Effect estimates obtained by a multivariate analysis of total and specific IgE values in 18,085 individuals also excluded major birth month effects and confirmed the independent effect of language grouping. Conclusion Neither time point of first exposure to certain allergens nor early infections during winter months seems to be a major factor for adult allergy. Although there might be effects of climate or environmental UV exposure by latitude, influences within language groups seem to be more important, reflecting so far unknown genetic or cultural risk factors.
A Modern View of the Surgical Treatment of Peripheral Arterial Disease
Authors: D. Craig Miller
Journal: JAMA (1978)

As life expectancy increases, more patients will harbor atherosclerotic conditions that portend disability and death. Due basically to a communication gap, sizable numbers of these patients who stand to benefit from vascular reconstruction are not being referred or are being referred too late to vascular surgeons. Vascular surgery currently can save limbs, extend productivity and life expectancy, ameliorate hypertension, and prevent stroke more reliably and with less risk than ever before. As the subspeciality of vascular surgery has matured, has incorporated additional fellowship training, and now approaches potential recognition in some yet to be determined form by The American Board of Surgery, it is incumbent on general physicians and vascular surgeons alike to develop appropriate channels that can transmit clinical concepts, educational information, and clinical results, as well as refer patients.
Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival
Authors: Sang Soo Kang, Kyung-Seok Han, Bo Mi Ku, Yeon Kyung Lee, Jinpyo Hong, Hye Young Shin, Antoine G. Almonte, Dong Ho Woo, Daniel J. Brat, Eun Mi Hwang, Seung Hyun Yoo, Chun Kee Chung, Sung-Hye Park, Sun Ha Paek, Eun Joo Roh, Sung joong Lee, Jae-Yong Park, Stephen F. Traynelis, C. Justin Lee
Journal: Cancer Research (2010)

Calcium signaling is important in many signaling processes in cancer cell proliferation and motility including in deadly glioblastomas of the brain that aggressively invade neighboring tissue. We hypothesized that disturbing Ca(2+) signaling pathways might decrease the invasive behavior of giloblastoma, extending survival. Evaluating a panel of small-molecule modulators of Ca(2+) signaling, we identified caffeine as an inhibitor of glioblastoma cell motility. Caffeine, which is known to activate ryanodine receptors, paradoxically inhibits Ca(2+) increase by inositol 1,4,5-trisphospate receptor subtype 3 (IP(3)R3), the expression of which is increased in glioblastoma cells. Consequently, by inhibiting IP(3)R3-mediated Ca(2+) release, caffeine inhibited migration of glioblastoma cells in various in vitro assays. Consistent with these effects, caffeine greatly increased mean survival in a mouse xenograft model of glioblastoma. These findings suggest IP(3)R3 as a novel therapeutic target and identify caffeine as a possible adjunct therapy to slow invasive growth of glioblastoma.
ICAM-1 and integrin expression on isolated human alveolar type II pneumocytes
Authors: J Guzman, T Izumi, S Nagai, U Costabel
Journal: European Respiratory Journal (1994)

Adhesion molecules are involved in the recruitment of leucocytes to sites of inflammation. In this study, we determined the expression of several adhesion molecules on isolated human alveolar type II pneumonocytes. Type II pneumocytes were isolated from 10 normal lung specimens, by enzymatic digestion with dispase, followed by metrizamide gradient centrifugation and panning on immunoglobulin G (IgG)-coated plastic dishes. With the freshly isolated type II cells, immunostaining was performed using a sensitive immunoperoxidase slide technique. In all cases, 60-90% of type II cells were positive for intercellular adhesion molecule-1 (ICAM-1) (CD54). A minor portion of type II cells expressed the alpha 4 (CD49d) subunit of the beta 1-integrins, and the alpha-v (CD51) subunit of the vitronectin receptor. CD11a, CD11b, CD11c, CD18, CD49b, and CD49f failed to demonstrate any immunostaining with type II cells. In conclusion, the observation of the expression of ICAM-1 and, to a lesser degree, of some integrin subunits, may indicate that alveolar type II cells participate in local immune and inflammatory responses.
Effects of resistive load on performance and surface EMG activity during repeated cycling sprints on a non-isokinetic cycle ergometer
Authors: R Matsuura, T Arimitsu, T Yunoki, T Yano
Journal: British Journal of Sports Medicine (2009)

To determine the effects of resistive load on performance and surface electromyogram (SEMG) activity during repeated cycling sprints (RCS) on a non-isokinetic cycle ergometer.Participants performed two RCS tests (ten 10-second cycling sprints) interspersed with both 30- and 360-second recovery periods under light (RCS(L)) and heavy load conditions (RCS(H)) in a random counterbalanced order. Recovery periods of 360 seconds were set before the fifth and ninth sprints.In the 9th and 10th sprints, the values of peak power output divided by body mass were significantly higher in RCS(H) than in RCS(L). Changes in blood lactate concentration were not different between the two conditions. In RCS(L), the root mean square calculated from the SEMG was significantly lower in the ninth sprint than in the first sprint, but there were no differences between the root mean square in the first sprint and that in the ninth sprint in RCS(H).During RCS on a non-isokinetic cycle ergometer, performance and SEMG activity are influenced by resistive load. It is thought that regulation of skeletal muscle recruitment by the central nervous system is associated with fatigue during RCS with a light resistive load.
Prostate Cancer and Supplementation With α-Tocopherol and β-Carotene: Incidence and Mortality in a Controlled Trial
Authors: Olli P. Heinonen, Leopold Koss, Demetrius Albanes, Philip R. Taylor, Anne M. Hartman, Brenda K. Edwards, Jarmo Virtamo, Jussi K. Huttunen, Jaason Haapakoski, Nea Malila, Matti Rautalahti, Samuli Ripatti, Hanna Mäenpää, Lasse Teerenhovi, Martti Virolainen
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Epidemiologic studies have suggested that vitamin E and β-carotene may each influence the development of prostate cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of α-tocopherol (a form of vitamin E) and β-carotene supplementation, separately or together, on prostate cancer in male smokers. Methods: A total of 29 133 male smokers aged 50–69 years from southwestern Finland were randomly assigned to receive α-tocopherol (50 mg), β-carotene (20 mg), both agents, or placebo daily for 5–8 years (median, 6.1 years). The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated. Results: We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period. A 32% decrease (95% confidence interval [CI] = −47% to −12%) in the incidence of prostate cancer was observed among the subjects receiving α-tocopherol (n = 14 564) compared with those not receiving it (n = 14 569). The reduction was evident in clinical prostate cancer but not in latent cancer. Mortality from prostate cancer was 41% lower (95% CI = −65% to −1%) among men receiving α-tocopherol. Among subjects receiving β-carotene (n = 14 560), prostate cancer incidence was 23% higher (95% CI = −4%–59%) and mortality was 15% higher (95% CI = −30%–89%) compared with those not receiving it (n = 14 573). Neither agent had any effect on the time interval between diagnosis and death. Conclusions: Long-term supplementation with α-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers. Other controlled trials are required to confirm the findings.
Lidocaine Action on Na <sup>+</sup> Currents in Ventricular Myocytes From the Epicardial Border Zone of the Infarcted Heart
Authors: Jielin Pu, Jeffrey R. Balser, Penelope A. Boyden
Journal: Circulation Research (1998)

Abstract —Myocytes overlying a zone of infarction form the primary substrate for serious reentrant ventricular arrhythmias. In vitro and in vivo studies suggest that antiarrhythmic agents affect Na + channels of cells from the epicardial border zone (EBZ) of the 5-day infarcted heart differently than they affect those of normal muscle. However, the mechanisms responsible for this difference remain unclear. Previous studies have revealed differences in Na + current ( I Na ) density and inactivation gating kinetics in myocytes dispersed from the EBZ (IZs). Since changes in inactivation gating could influence lidocaine action, we examined the effects of lidocaine on I Na of IZs (n=38) and epicardial myocytes from the noninfarcted heart (NZs) (n=50) using the whole-cell variation of the patch-clamp technique. In drug-free conditions, the voltage dependence of steady-state inactivation of IZs was shifted negative to that of NZs, causing greater inactivation of IZ channels at depolarized (≥−100-mV) holding potentials. Consistent with a high affinity for the inactivated channel conformation, lidocaine produced more tonic block in IZs than NZs at depolarized holding potentials. Additionally, in drug-free conditions, IZ I Na exhibited an enhanced rate of inactivation from closed states, a delay in recovery from inactivation, and increased use-dependent reduction in amplitude during rapid (1- to 3-Hz) pulse trains. In both IZs and NZs, lidocaine (20 to 120 μmol/L) accelerated the rate of time-dependent loss of availability and markedly delayed recovery from availability, inducing significant use-dependent reduction of I Na . However, at drug concentrations ≥60 μmol/L, the difference in use-dependent current reduction between IZs and NZs was minimized. The action of lidocaine to render Na + channel inactivation in NZs more similar to that of IZs may be central to its (pro)antiarrhythmic effects.
A Quantitative Angiocardiographic Study of Left Ventricular Hypertrophy and the Electrocardiogram
Authors: WILLIAM A. BAXLEY, HAROLD T. DODGE, HAROLD SANDLER
Journal: Circulation (1968)

The QRS amplitude, duration, and mean axis direction of the standard 12-lead electrocardiogram were compared with left ventricular mass, volume, wall thickness, and stroke work in 112 adult patients. These patients had normal left ventricles or various degrees of left ventricular dilatation or hypertrophy. Left ventricular volumes and mass were determined by a quantitative angiocardiographic method. A significant but not a close correlation between left ventricular mass and ECG voltage was found. Enddiastolic volume, stroke volume, stroke work, wall thickness, and "total left ventricular volume" (volume of left ventricular muscle and cavity at end-diastole) had generally lesser degrees of correlation with the QRS amplitude than did the mass alone. Subgrouping of patients into those with pressure overload on the left ventricle, volume overload, aortic valve disease, or anatomic left ventricular hypertrophy did not improve correlations. The left ventricular hypertrophy voltage criteria of Sokolow and of Grant were assessed; respectively, 68% and 67% of 75 patients with anatomic hypertrophy had hypervoltage. The direction of the anatomic long axis of the left ventricle was not significantly related to the mean QRS-vector direction.
Incomprehensible consent forms:Child friendly consent forms lead the way
Authors: Katherine Curtis, Helen Roberts
Journal: BMJ (2005)

The General Medical Council and the future of revalidation GMC member respondsEditor-Esmail and Kmietowicz give an inaccurate account of the General Medical Council's policy development on revalidation, ignoring an iterative process with interested parties since 1998 in an attempt to introduce the most fundamental change to medical regulation since its foundation in 1858. 1 2 The GMC clearly has had regard to the legitimate interests of three principal groups-government and the NHS, patients and the public, and the various tribes that make up the UK medical profession.Despite suggestions to the contrary, an initial exploratory meeting on revalidation convened by Sir Donald Irvine in June 1998 was held in the context of a high profile professional conduct case, but well before the Bristol inquiry report and absolutely nothing to do with Rodney Ledward or, indeed, Harold Shipman.It was recognised then that some doctors were not keeping fully up to date nor were they indulging in reflective practice.Irvine correctly proposed that there was a need to make registration with the GMC more meaningful to the public than a mere recognition that doctors had reached a certain standard of professional knowledge in their early 20s.Both articles promote the idea that the doctors' regulator should be filling the vacuum within the NHS created by its failing to fulfil its public responsibility to monitor doctors' clinical standards.Clinical governance is now, slowly, being developed and eventually will extend from systems and teams to individuals-but is it reasonable, as both authors postulate, that such monitoring should become the financial and moral responsibility of the GMC sitting in London and Manchester rather than local managers at the coalface?Although revalidation is a continuing process, it becomes summative only every five years.The NHS and its local systems must not be allowed to abrogate their responsibility for the safety of patients on a day to day basis.Nor should they demand that the GMC and its prime function of assuring fitness to practise and the meaning of the medical register be inappropriately promoted as the first line of defence for the maintenance of clinical quality and safety.
Cost-effectiveness of Population Screening for BRCA Mutations in Ashkenazi Jewish Women Compared With Family History–Based Testing
Authors: Ranjit Manchanda, Rosa Legood, Matthew Burnell, Alistair McGuire, Maria Raikou, Kelly Loggenberg, Jane Wardle, Saskia Sanderson, Sue Gessler, Lucy Side, Nyala Balogun, Rakshit Desai, Ajith Kumar, Huw Dorkins, Yvonne Wallis, Cyril Chapman, Rohan Taylor, Chris Jacobs, Ian Tomlinson, Uziel Beller, Usha Menon, Ian Jacobs
Journal: JNCI Journal of the National Cancer Institute (2014)

Population-based testing for BRCA1/2 mutations detects the high proportion of carriers not identified by cancer family history (FH)-based testing. We compared the cost-effectiveness of population-based BRCA testing with the standard FH-based approach in Ashkenazi Jewish (AJ) women.A decision-analytic model was developed to compare lifetime costs and effects amongst AJ women in the UK of BRCA founder-mutation testing amongst: 1) all women in the population age 30 years or older and 2) just those with a strong FH (≥10% mutation risk). The model assumes that BRCA carriers are offered risk-reducing salpingo-oophorectomy and annual MRI/mammography screening or risk-reducing mastectomy. Model probabilities utilize the Genetic Cancer Prediction through Population Screening trial/published literature to estimate total costs, effects in terms of quality-adjusted life-years (QALYs), cancer incidence, incremental cost-effectiveness ratio (ICER), and population impact. Costs are reported at 2010 prices. Costs/outcomes were discounted at 3.5%. We used deterministic/probabilistic sensitivity analysis (PSA) to evaluate model uncertainty.Compared with FH-based testing, population-screening saved 0.090 more life-years and 0.101 more QALYs resulting in 33 days' gain in life expectancy. Population screening was found to be cost saving with a baseline-discounted ICER of -£2079/QALY. Population-based screening lowered ovarian and breast cancer incidence by 0.34% and 0.62%. Assuming 71% testing uptake, this leads to 276 fewer ovarian and 508 fewer breast cancer cases. Overall, reduction in treatment costs led to a discounted cost savings of £3.7 million. Deterministic sensitivity analysis and 94% of simulations on PSA (threshold £20000) indicated that population screening is cost-effective, compared with current NHS policy.Population-based screening for BRCA mutations is highly cost-effective compared with an FH-based approach in AJ women age 30 years and older.
Ether à go-go potassium channel expression in soft tissue sarcoma patients
Authors: Fernanda Mello de Queiroz, Guilherme Suarez-Kurtz, Walter Stühmer, Luis A Pardo
Journal: Molecular Cancer (2006)

Abstract Background The expression of the human Eag1 potassium channel (Kv10.1) is normally restricted to the adult brain, but it has been detected in both tumour cell lines and primary tumours. Our purpose was to determine the frequency of expression of Eag1 in soft tissue sarcoma and its potential clinical implications. Results We used specific monoclonal antibodies to determine the expression levels of Eag1 in soft tissue sarcomas from 210 patients by immunohistochemistry. Eag1 was expressed in 71% of all tumours, with frequencies ranging from 56% (liposarcoma) to 82% (rhabdomyosarcoma). We detected differences in expression levels depending on the histological type, but no association was seen between expression of this protein and sex, age, grade or tumour size. Four cell lines derived from relevant sarcoma histological types (fibrosarcoma and rhabdomyosarcoma) were tested for Eag1 expression by real-time RT-PCR. We found all four lines to be positive for Eag1. In these cell lines, blockage of Eag1 by RNA interference led to a decrease in proliferation. Conclusion Eag1 is aberrantly expressed in over 70% sarcomas. In sarcoma cell lines, inhibition of Eag1 expression and/or function leads to reduced proliferation. The high frequency of expression of Eag1 in primary tumours and the restriction of normal expression of the channel to the brain, suggests the application of this protein for diagnostic or therapeutic purposes.