tbuckley/cabot-search huggingface dataset:
CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity.
Authors: H A Pereira, W M Shafer, J Pohl, L E Martin, J K Spitznagel
Journal: Journal of Clinical Investigation (1990)

CAP37, an antimicrobial protein of human neutrophil granules, is a specific chemoattractant for monocytes. Purified to homogeneity by sequential chromatography over carboxymethyl Sephadex, G-75 Sephadex, and hydrophobic interaction HPLC, demonstratively endotoxin-free CAP37 was maximally chemotactic over a range of 1.3 X 10(-9)-10(-8) M. Thus it was active in the same molar concentrations as formyl-methionyl-leucyl-phenylalanine. CAP37 lacked chemotactic activity for neutrophils and lymphocytes. In checkerboard assays CAP37 had some chemokinetic activity as well. It was also chemotactic for rabbit mononuclear cells. Higher concentrations (2.7 X 10(-8) M) were required for activity with rabbit cells than with human. Sequence analysis of the first 42 NH2-terminal amino acid residues of CAP37 showed strong homologies with known serine proteases that mediate various functions in inflammation. However, a critical substitution of a serine for a histidine at position 41 suggested that CAP37 lacked serine protease action. This impression was supported by the failure of CAP37 to bind tritiated diisopropyl fluorophosphate. 89% of total CAP37 was released extracellularly from human neutrophils while they phagocytized Staphylococcus aureus. We propose that CAP37 released from neutrophils during phagocytosis and degranulation may mediate recruitment of monocytes in the second wave of inflammation.
Association of a pool of HIV-1 with erythrocytes in vivo: a cohort study
Authors: Christoph Hess, Thomas Klimkait, Luregn Schlapbach, Veronika Del Zenero, Salima Sadallah, Eliska Horakova, Gianmarco Balestra, Verena Werder, Christoph Schaefer, Manuel Battegay, Jürg-Alfred Schifferli
Journal: The Lancet (2002)
Increased incidence of pulmonary tuberculosis in chronic interstitial lung disease.
Authors: Y Shachor, D Schindler, A Siegal, D Lieberman, Y Mikulski, I Bruderman
Journal: Thorax (1989)

Of 162 patients with chronic interstitial lung disease, eight (seven of them male) had active tuberculosis. This was 4.5 times higher than the incidence in the general population. The frequency of tuberculosis was similar in patients treated with and without corticosteroids.
Evidence for Hemodynamic Autoregulation of Renin Release
Authors: IVAR EIDE, EINAR LOslash;YNING, FREDRIK KIIL
Journal: Circulation Research (1973)

To examine the relationship between renal arteriolar dilatation and renin release, arterial perfusion pressure in anesthetized dogs was lowered in steps within and below the range of autoregulation of renal blood flow. Renin release, determined by both bioassay and radioimmunoassay, averaged 2.7 ± 0.9 ( SE ) µg/min at control pressure and increased to 20.0 ± 4.1 ( SE ) µg/min at the lowest autoregulating pressure, which averaged 66.4 ± 2.9 ( SD ) mm Hg. However, renin release then remained constant during further lowering of arterial perfusion pressure despite reductions in renal blood flow. This response was not significantly changed when sodium excretion was increased by intravenous infusion of mannitol. In another series of experiments, renin release was raised by reducing arterial perfusion pressure below the range of autoregulation, and control sodium excretion was reestablished by mannitol or saline infusion; renin release remained high. Therefore, renin release appears to be related to autoregulated dilatation of the renal arterioles, and it becomes maximal when the arterioles are completely dilated at the lowest pressure of autoregulation of renal blood flow. This mechanism is different from release mechanisms dependent on sodium delivery to the distal nephron.
The Phosphoinositide 3-Kinase/Akt1/Par-4 Axis: A Cancer-Selective Therapeutic Target
Authors: Anindya Goswami, Padhma Ranganathan, Vivek M. Rangnekar
Journal: Cancer Research (2006)

Abstract Activation of the phosphoinositide 3-kinase (PI3K)/Akt cell survival pathway in many cancers makes it an appealing target for therapeutic development. However, because this pathway also has an important role in the survival of normal cells, tactics to achieve cancer selectivity may prove important. We recently showed that the cancer-selective proapoptotic protein Par-4 is a key target for inactivation by PI3K/Akt signaling. Additionally, we found that Par-4 participates in mediating apoptosis by PTEN, the tumor suppressor responsible for blocking PI3K/Akt signaling. As a central player in cancer cell survival, Par-4 may provide a useful focus for the development of cancer-selective therapeutics. (Cancer Res 2006; 66(6): 2889-92)
Mild cervical cytological abnormalities.
Authors: M. I. Shafi, D. M. Luesley, J. A. Jordan
Journal: BMJ (1992)

Group these radical changes mean fighting on three fronts.The first will be a battle within Whitehall for the resources to do the job properly, in a way that really will mean improvements for Londoners in the next century and a strengthening of the city as an international centre for research and medical education.The second will be with the managements and workforces of individual institutions, most of whom recognise that changes are needed but cannot accept that these must affect them.The third is with streetwise and sceptical Londoners, all of whom identify with "their" hospital and have profound reservations about the proposed changes.
Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening
Authors: Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Anne Dawnay, Mariam Habib, Sophia Apostolidou, Naveena Singh, Elizabeth Benjamin, Matthew Burnell, Susan Davies, Aarti Sharma, Richard Gunu, Keith Godfrey, Alberto Lopes, David Oram, Jonathan Herod, Karin Williamson, Mourad W. Seif, Howard Jenkins, Tim Mould, Robert Woolas, John B. Murdoch, Stephen Dobbs, Nazar N. Amso, Simon Leeson, Derek Cruickshank, Ian Scott, Lesley Fallowfield, Martin Widschwendter, Karina Reynolds, Alistair McGuire, Stuart Campbell, Mahesh Parmar, Steven J. Skates, Ian Jacobs
Journal: Journal of Clinical Oncology (2015)

Purpose Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. Patients and Methods In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. Results After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). Conclusion Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.
Highly potent and selective inhibition of varicella‐zoster virus replication by bicyclic furo[2,3‐d]pyrimidine nucleoside analogues
Authors: Erik De Clercq
Journal: Medicinal Research Reviews (2003)

Abstract The bicyclic furo[2,3‐ d ]pyrimidine nucleoside analogues represent an entirely new class of fused furopyrimidine derivatives with unprecedented selectivity for varicella‐zoster virus (VZV). From extensive structure‐activity relationship (SAR) studies, the 6‐( p ‐alkylphenyl)substituted furopyrimidine derivatives Cf 1742 and Cf 1743 emerged as the most potent inhibitors of VZV replication: they were found to inhibit both laboratory VZV strains and clinical VZV isolates at subnanomolar concentrations, while not being toxic to the host cells at 100,000‐fold higher concentrations. Although the precise mechanism of action of these compounds remains to be elucidated, it is clear that for their antiviral activity they depend on phosphorylation by the VZV‐encoded thymidine kinase. The furo[2,3‐ d ]pyrimidine nucleoside analogues are not susceptible to degradation by human or bacterial thymidine phosphorylase, which may otherwise release the free aglycone. Also, the latter is not inhibitory to dihydropyrimidine dehydrogenase, an enzyme involved in the degradation of thymine, uracil, and the anticancer agent 5‐fluorouracil. Further development of the furo[2,3‐ d ]pyrimidine nucleoside analogues as new therapeutic modalities for the treatment of VZV infections (i.e., varicella and herpes zoster) seems highly justified. © 2003 Wiley Periodicals, Inc. Med Res Rev. 23, No. 3, 253–274, 2003
Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial
Authors: C. Grootscholten, G. Ligtenberg, E.C. Hagen, A.W.L. van den Wall Bake, J.W. de Glas-Vos, M. Bijl, K.J. Assmann, J.A. Bruijn, J.J. Weening, H.C. van Houwelingen, R.H.W.M. Derksen, J.H.M. Berden
Journal: Kidney International (2006)
Quantitative analysis of the effect of tubulin isotype expression on sensitivity of cancer cell lines to a set of novel colchicine derivatives
Authors: Chih-Yuan Tseng, Jonathan Y Mane, Philip Winter, Lorelei Johnson, Torin Huzil, Elzbieta Izbicka, Richard F Luduena, Jack A Tuszynski
Journal: Molecular Cancer (2010)

Abstract Background A maximum entropy approach is proposed to predict the cytotoxic effects of a panel of colchicine derivatives in several human cancer cell lines. Data was obtained from cytotoxicity assays performed with 21 drug molecules from the same family of colchicine compounds and correlate these results with independent tubulin isoform expression measurements for several cancer cell lines. The maximum entropy method is then used in conjunction with computed relative binding energy values for each of the drug molecules against tubulin isotypes to which these compounds bind with different affinities. Results We have found by using our analysis that αβ I and αβ III tubulin isoforms are the most important isoforms in establishing predictive response of cancer cell sensitivity to colchicine derivatives. However, since αβ I tubulin is widely distributed in the human body, targeting it would lead to severe adverse side effects. Consequently, we have identified tubulin isotype αβ III as the most important molecular target for inhibition of microtubule polymerization and hence cancer cell cytotoxicity. Tubulin isotypes αβ I and αβ II are concluded to be secondary targets. Conclusions The benefit of being able to correlate expression levels of specific tubulin isotypes and the resultant cell death effect is that it will enable us to better understand the origin of drug resistance and hence design optimal structures for the elimination of cancer cells. The conclusion of the study described herein identifies tubulin isotype αβ III as a target for optimized chemotherapy drug design.
Changes in Cortical Functioning With Acute Hypoglycemia and Hyperglycemia in Type I Diabetes
Authors: Richard G Hoffman, Diana J Speelman, Deborah A Hinnen, Kirby L Conley, Richard A Guthrie, Robert K Knapp
Journal: Diabetes Care (1989)

In this study, 18 type I (insulin-dependent) diabetic subjects aged 22–35 yr (mean age 29.3) and within 10 yr of diagnosis (mean 7.7) performed a battery of cognitive and psychomotor tasks under conditions of hypoglycemia (50 mg/dl), normoglycemia (100 mg/dl), and hyperglycemia (300 mg/dl). Blood glucose levels during testing were precisely maintained at the preselected level via a Biostator insulin/glucose-infusion system. The order of glycemic level was counterbalanced across subjects in a single-blinded design. Performance on tasks requiring visual tracking, visuomotor speed, concentration, and planning ability (pursuit rotor and trails B) were significantly impaired under conditions of hypoglycemia compared with normoglycemic levels. Visual reaction time was not significantly impaired under conditions of hypoglycemia or hyperglycemia.
Therapeutic advances in non-small cell lung cancer
Authors: Eric Vallières, Solange Peters, Paul Van Houtte, Paras Dalal, Eric Lim
Journal: Thorax (2011)

Despite decades of research, therapeutic advances in non-small cell lung cancer (NSCLC) have progressed at a painstaking slow rate with few improvements in standard surgical resection for early stage disease and chemotherapy or radiotherapy for patients with advanced disease. In the past 18 months, however, we seemed to have reached an inflexion point: therapeutic advances that are centred on improvements in the understanding of patient selection, surgery that is undertaken through smaller incisions, identification of candidate mutations accompanied by the development of targeted anticancer treatments with a focus on personalised medicine, improvements to radiotherapy technology, emergence of radiofrequency ablation (RFA), and last but by no means least, the recognition of palliative care as a therapeutic modality in its own right. The contributors to this review are a distinguished international panel of experts who highlight recent advances in each of the major disciplines.
Expression of IL-32 in Human Lung Cancer Is Related to the Histotype and Metastatic Phenotype
Authors: Carlo Sorrentino, Emma Di Carlo
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: A strong link has been recently demonstrated between inflammation and lung cancer. Thus, we investigated whether the proinflammatory cytokine IL-32 may be involved in lung carcinogenesis and hence provide a novel therapeutic target.Objectives: Lung cancer subtypes display different clinical outcomes. We have set out to clarify the role of IL-32 in the physiopathology of the main histotypes.Methods: IL-32 expression, as visualized by immunohistochemistry on 23 premalignant and 148 malignant lesions, was correlated with clinicopathological and survival data. Confocal microscopy, microdissection, and real-time reverse transcription–polymerase chain reaction were used to identify cell sources and expression levels of IL-32.Measurements and Main Results: IL-32 expression was lacking in the majority of squamous-cell carcinomas (SCC) (76%) and their precursor lesions, but strongly up-regulated in most adenocarcinomas (AC) (73%) and their precursors, 64% of large-cell carcinomas, and 77% of small-cell lung cancers. Lymph node metastases frequently developed from IL-32–expressing lung cancers, and especially (82%) from those endowed with an IL-32–expressing leukocyte infiltrate (TIL) mainly composed of CD68+ macrophages, CD4+ T lymphocytes, and DC-SIGN+ dendritic cells. Expression levels of IL-32 by both TIL and tumor cells (TC), particularly in AC and SCC, were paralleled by those of IL-6, IL-8, and vascular endothelial growth factor in the same cell population and correlated with high intratumor microvessel density and poor clinical outcome.Conclusions: IL-32 is probably implicated in the pathogenesis of most lung cancer histotypes but unlikely in that of SCC. Its TIL and TC expression are both associated with acquisition of an invasive and metastatic phenotype and may be a useful prognostic indicator.
Status Syndrome: How Your Social Standing Directly Affects Your Health and Life Expectancy
Authors: Roberto De Vogli
Journal: BMJ (2004)

In affluent nations, an individual's position in the social hierarchy is increasingly recognised as one of the major determinants of health. People who are lower in the hierarchy tend to have worse health and shorter life expectancy. Michael Marmot argues that low social standing is seen not only as a condition of material deprivation but also as an indicator of people's capability to control life and fully participate in society (psychosocial disadvantage). As a person's position in the social hierarchy decreases, the less likely he or she is to have full control over life and opportunities for full participation in society.
Regression of Latent Endometrial Precancers by Progestin Infiltrated Intrauterine Device
Authors: Anne Ørbo, Cecil E. Rise, George L. Mutter
Journal: Cancer Research (2006)

Abstract PTEN tumor suppressor inactivation is the earliest step in endometrial carcinogenesis, occurring in morphologically unremarkable endometrial glands in half of normal women. We test the hypothesis that sex hormones positively or negatively select for these “latent precancers” by examining their emergence, persistence, and regression rates under differing hormonal conditions. Perimenopausal and postmenopausal women had an intake endometrial biopsy and underwent hormonal therapy with progestin-impregnated intrauterine device (IUD; n = 21), cyclic oral progestins (n = 28), or surveillance only (n = 22) with follow-up biopsies. For comparison, premenopausal naturally cycling endometrial biopsies were studied as single time points in 87 patients and multiple surveillance time points in 34 patients. Biopsies in which any PTEN protein-null glands were found by immunohistochemistry were scored as containing a latent endometrial precancer. All groups had a similar proportion of latent precancers at intake but differed after therapy. Emergence rates were highest (21%) for the naturally cycling premenopausal group compared with just 9% for untreated perimenopausal women. The IUD group had the highest rate of regression, with a 62% pretherapy and 5% post-therapy rate of latent precancers. This contrasted to nonsignificant changes for the oral progestin and untreated control groups. Delivery of high doses of progestins locally to the endometrium by IUD leads to ablation of preexisting PTEN-inactivated endometrial latent precancers and is a possible mechanism for reduction of long-term endometrial cancer risk known to occur in response to this hormone. (Cancer Res 2006; 66(11): 5613-7)
Granulomatous bronchiolitis of Crohn's disease successfully treated with inhaled budesonide
Authors: T K Trow, D G Morris, C R Miller, R J Homer
Journal: Thorax (2009)

A 39-year-old white woman with longstanding Crohn’s disease presented with the rare complication of granulomatous bronchiolitis. Rapid resolution after inhaled budesonide is highlighted, as this is the first case described in the literature successfully treated without the need for systemic therapy. This less toxic approach to therapy is warranted in granulomatous bronchiolitis of Crohn’s disease to avoid unwanted side effects of steroids and infliximab.
Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies
Authors: Steven D Schwartz, Carl D Regillo, Byron L Lam, Dean Eliott, Philip J Rosenfeld, Ninel Z Gregori, Jean-Pierre Hubschman, Janet L Davis, Gad Heilwell, Marc Spirn, Joseph Maguire, Roger Gay, Jane Bateman, Rosaleen M Ostrick, Debra Morris, Matthew Vincent, Eddy Anglade, Lucian V Del Priore, Robert Lanza
Journal: The Lancet (2014)
Characterization of the Hyperpolarization-Activated Current, I <sub>f</sub> , in Ventricular Myocytes From Human Failing Heart
Authors: Elisabetta Cerbai, Roberto Pino, Francesco Porciatti, Guido Sani, Michele Toscano, Massimo Maccherini, Gabriele Giunti, Alessandro Mugelli
Journal: Circulation (1997)

Background Disease-associated electrophysiological alterations may contribute to the increased predisposition to arrhythmias of the hypertrophied or failing myocardium. An I f -like current is expressed in rat left ventricular myocytes (LVMs), its amplitude being linearly related to the severity of cardiac hypertrophy. Here, we report the occurrence and electrophysiological properties of I f in human LVMs. Methods and Results LVMs were isolated from hearts of three male patients undergoing cardiac transplantation for terminal heart failure due to ischemic dilated cardiomyopathy. The patch-clamp technique was used to record I f , ie, a barium-insensitive, cesium-sensitive, time-dependent increasing inward current elicited on hyperpolarization. Membrane capacitance was 244±27 pF (n=25). I f occurred in all cells tested; its density measured at −120 mV was 2.1±0.3 pA/pF. Activation curves of I f (n=24) were fitted by a Boltzmann function; the threshold was −55 mV; midpoint, −70.9±2.1 mV; slope, −5.4±0.3 mV; and maximal specific conductance, 19.6±2.5 pS/pF. I f blockade by extracellular cesium was voltage dependent. Reducing extracellular potassium concentration from 25 to 5.4 mmol/L caused a shift of the reversal potential from −12.7±0.5 to −24.8±2.1 mV and a 64% decrease of current conductance. Conclusions I f is present in human LVMs. Its electrophysiological characteristics resemble those previously described in hypertrophied rat LVMs and suggest that I f could be an arrhythmogenic mechanism in patients with severe heart failure.
Treatment of Helicobacter pylori: future therapeutic and prophylactic perspectives
Authors: A T R Axon
Journal: Gut (1998)

Helicobacter is one of the most widespread, chronic infections in the world and causes a serious disease with a significant mortality.The organism is diYcult to eradicate using antibiotic therapy and to date no vaccine is available for use in humans.The most successful treatments comprise acid suppression in combination with two antibiotics and a series of seven day courses will reliably cure around 85% of infected individuals.Further modifications of these regimens via the introduction of newer and more eVective antibiotics and acid suppressants may enable the treatment to be simplified, made more eVective and cause fewer side eVects.However, the major challenge is to develop a specific monotherapy targeted against Helicobacter pylori.The H pylori genome has now been sequenced and this provides an opportunity both to identify specific targets for drug therapy, and to facilitate the identification and production of antigens that may be helpful in manufacturing a vaccine.This paper discusses the future of helicobacter therapy and vaccination.
The gap into dissolution: The real story
Authors: Martin Kurthen
Journal: Behavioral and Brain Sciences (1999)

For a theory of phenomenal consciousness, the real issue is not that between vehicle and process, but between naturalistic and deconstructive theories. Most current naturalistic theories combine a hypothesis about the neural correlate of consciousness with a subsequent naturalistic proposal about how to close the explanatory gap. Deconstructive theories use theses about the neural correlate of consciousness only to motivate and support their claim that the “hard problem” of consciousness is a pseudo-problem which is not to be solved, but rather dissolved on non-naturalistic grounds. O'Brien &amp; Opie present a hypothesis concerning the neural correlate of consciousness, but no genuine strategy to close the explanatory gap. Their theory can, however, contribute to the success of a deconstructive theory of PC.